April 2003 $4.95

SOLVING THE NEUTRINO MYSTERY • RECOGNIZING ANCIENT LIFE

APRIL 2003 $4.95 WWW.SCIAM.COM

James D.Watson discusses DNA, the brain, designer babies and more as he reﬂects on

Grid Computing’s Unbounded Potential

Ginkgo Biloba Will Mount Etna and Memory Explode Tomorrow?

Delivering Drugs with Implanted Chips

COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. april 2003 contentsSCIENTIFIC AMERICAN Volume 288 Number 4 features ASTROPHYSICS 40 Solving the Solar Neutrino Problem BY ARTHUR B. MCDONALD, JOSHUA R. KLEIN AND DAVID L. WARK After 30 years, physicists fathom the mystery of the missing neutrinos: the phantom particles change en route from the sun.

BIOTECHNOLOGY 50 Where a Pill Won’t Reach BY ROBERT LANGER Implanted microchips, embedded polymers and ultrasonic blasts of proteins will deliver next-generation medicines. 66 James D. Watson VOLCANOLOGY 58 Mount Etna’s Ferocious Future BY TOM PFEIFFER Europe’s most active volcano grows more dangerous, but slowly.

CELEBRATING THE GENETIC JUBILEE 66 A Conversation with James D. Watson The co-discoverer of DNA’s double helix reﬂects on the molecular model that changed both science and society.

LIFE SCIENCE 70 Questioning the Oldest Signs of Life BY SARAH SIMPSON Researchers are reevaluating how they identify traces left by life in ancient rocks on earth—and elsewhere in the solar system.

INFORMATION TECHNOLOGY 78 The Grid: Computing without Bounds BY IAN FOSTER Powerful global networks of processors and storage may end the era of self-contained computing.

MEDICINE 86 The Lowdown on Ginkgo Biloba BY PAUL E. GOLD, LARRY CAHILL AND GARY L. WENK This herbal supplement may slightly improve your memory—but so can eating a candy bar. Also: Mark A. McDaniel, Steven F. Maier and Gilles O. Einstein discuss other “brain boosters.”

www.sciam.com SCIENTIFIC AMERICAN 7 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. departmentsSCIENTIFIC AMERICAN Volume 288 Number 4 10 SA Perspectives Get real about abstract worries. 12 How to Contact Us 12 On the Web 28 100 16 Letters 20 50, 100 & 150 Years Ago 22 News Scan 34 Innovations Metanomics develops a way to peek ■ Manned spaceﬂight after Columbia. into plant metabolism. ■ Spilled oil off Spain’s coast proves too slippery to predict. 37 Staking Claims ■ Bacteria thawed an ancient earth. The case for restricting patents that hinder basic ■ Suspicions about the speed of gravity. biomedical research. ■ Do gray wolves still need protection? 92 Working Knowledge ■ More proof that “clone” doesn’t mean “copy.” Patches that deliver drugs. ■ By the Numbers: Poverty in the U.S. ■ Data Points: Invasive species. 94 Technicalities Tablet PCs are high-tech tools for scribblers. 97 Reviews Faster Than the Speed of Light looks provocatively at the new cosmology. 94 columns 38 Skeptic BY MICHAEL SHERMER The Three Laws of Cloning. 100Puzzling Adventures BY DENNIS E. SHASHA Graphing the origins of species. 102 Anti Gravity BY STEVE MIRSKY Burgers and joints. 103Ask the Experts What is the importance of the new discovery? 104Fuzzy Logic BY ROZ CHAST

Cover image by Mike Medicine Horse, Hybrid Medical Animation

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Get Real

When the cloning of a human was announced last The answer from technocynics is yes. In his book last December, political and spiritual leaders condemned year Fukuyama drew a line between medical therapy it as an affront to the “dignity of man.” That kind of (OK) and genetic enhancement (not OK) but went on rhetoric is popping up all over the place. Political sci- to advocate a ban on all cloning, even the therapeutic entist Francis Fukuyama warns that genetic engineer- kind. Similarly, Joy has called for a “relinquishment” ing and Prozac-like drugs augur “a ‘posthuman’ stage of all—all—research into robotics, nanotechnology of history.” Bill Joy, co-founder of Sun Microsystems, and genetic engineering. Where does this absolutist frets over robotics and nanotechnology: “On this path stand leave the rest of us? We have watched our par- our humanity may well be lost.” ents and grandparents waste away from cancer and Even the Economist, a magazine Alzheimer’s disease. We have seen children die of dia- not usually given to apocalyptic betes and friends fall to depression, malaria and HIV. predictions, worries that neuro- If it comes down to a choice between the vague unease science could “gut the concept of that emerging technologies conjure up or the very un- human nature.” vague suffering they could cure, we know how we Like their counterparts in would decide. earlier ages, these commentators The technocynics basically want us to grin and bear argue that technology is running it, lest our attempts at self-improvement do more harm ahead of our ability to deal with than good. Yet if history is any guide, fears about the ANXIETY over genetically it; although scientiﬁc progress is impact of new technologies generally wind up sound- modified food often reflects all well and good, we have to rein ing pretty silly. Thoreau regarded trains, telegraphs, abstract worries about science. it in. Such views are often called newspapers and even mail delivery as dehumanizing. neo-Luddism, but frankly, that Late Victorians predicted that industrialization and ur- does not do justice to the Luddites. Those machine- banization would cause our species to degenerate to a smashing textile workers were reacting to immediate prehuman state. In the 1970s critics of in vitro fertil- threats, such as losing their jobs. Today’s concerns ization said it would create monstrous or deranged ba- tend to be abstract, and that is their problem. bies. In all these cases, abstract worries gave way to A science magazine is all in favor of abstract think- mundane ones. New technologies did bring new probing, but at some point abstraction needs to make con- lems, but people worked around them. Few would, in tact with reality. And the reality of research bears little retrospect, ditch the technologies altogether. resemblance to the technocynics’ horror stories. Will The biggest danger, then, is not that science will run cloning, for example, open the door to “designer ba- ahead of ethics, but the opposite: that ethical hair trig- bies”? Maybe one day. For now, though, researchers gers will paralyze worthy research. Striking a balance are struggling to develop cloning just to grow tissues that is not easy. Bioethicist Gregory Stock offers a sound

a patient’s immune system won’t reject. Even would-be prescription: “We should deal with actual rather than Corbis Sygma baby cloners don’t purport to ﬁddle with the genome. imagined problems.” To stop research is to give up try- Are people supposed to give up the prospect of life- ing to make the world a better place. It denies human

saving therapies to avoid a distant, hypothetical threat? nature in order to save it. SION TOUHIG

THE EDITORS [email protected]

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12 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. ® Letters EDITORS@ SCIAM.COM Established 1845 EDITOR IN CHIEF: John Rennie IF APRIL IS THE CRUELEST MONTH, December may EXECUTIVE EDITOR: Mariette DiChristina make us feel the most reflective, as we recall the past MANAGING EDITOR: Ricki L. Rusting NEWS EDITOR: Philip M. Yam year’s events. So it was with the December 2002 Per- SPECIAL PROJECTS EDITOR: Gary Stix spectives, “In Science We Trust.” The column reviewed REVIEWS EDITOR: Michelle Press SENIOR WRITER: W. Wayt Gibbs some of the achievements—and regrettable setbacks—of EDITORS: Mark Alpert, Steven Ashley, science, which the editors nonetheless praised for “its in- Graham P. Collins, Carol Ezzell, cremental progress toward a more complete understand- Steve Mirsky, George Musser CONTRIBUTING EDITORS: Mark Fischetti, ing of the observable world.” The commentary resonated Marguerite Holloway, Michael Shermer, with many, including James Edgar of Melville, Saskatch- Sarah Simpson, Paul Wallich ewan, who responded: “I think I’ll photocopy your editori- EDITORIAL DIRECTOR, ONLINE: Kate Wong ASSOCIATE EDITOR, ONLINE: Sarah Graham al and add it to my collection of wise words—a collection WEB DESIGN MANAGER: Ryan Reid that helps me to explain my beliefs about science, astronomy, evolution and life.” Other ART DIRECTOR: Edward Bell writers express their beliefs concerning the December issue on the following pages. SENIOR ASSOCIATE ART DIRECTOR: Jana Brenning ASSISTANT ART DIRECTORS: Johnny Johnson, Mark Clemens PHOTOGRAPHY EDITOR: Bridget Gerety POLLOCK’S FRACTALS PRODUCTION EDITOR: Richard Hunt I don’t understand some aspects of “Order in Pollock’s Chaos,” by Richard COPY DIRECTOR: Maria-Christina Keller P. Taylor. If the computer measures squares in Jackson Pollock’s works that have COPY CHIEF: Molly K. Frances COPY AND RESEARCH: Daniel C. Schlenoff, paint in them and those that don’t, I don’t think that the numerical ratio between Rina Bander, Shea Dean, Emily Harrison the haves and the have-nots would change, no matter the scale. EDITORIAL ADMINISTRATOR: Jacob Lasky The second thing that bothers me is the straight-line graph, when squares SENIOR SECRETARY: Maya Harty from 10 to zero millimeters are analyzed. Paintings are not like computer frac- ASSOCIATE PUBLISHER, PRODUCTION: William Sherman tals, in which the locations of edges can be determined at every scale. At such MANUFACTURING MANAGER: Janet Cermak ADVERTISING PRODUCTION MANAGER: Carl Cherebin sizes, I cannot imagine how one would know where the edge of the line is, giv- PREPRESS AND QUALITY MANAGER: Silvia Di Placido en that paint bleeds, runs, is absorbed by the surface and mixes with other col- PRINT PRODUCTION MANAGER: Georgina Franco PRODUCTION MANAGER: Christina Hippeli ors. It would seem, too, that the hills and valleys of the canvas would become CUSTOM PUBLISHING MANAGER: Madelyn Keyes-Milch the dominant features. Also, if a photograph of the painting was scanned into ASSOCIATE PUBLISHER/VICE PRESIDENT, CIRCULATION: the computer, doesn’t the analysis exceed the resolution capabilities of the pho- Lorraine Leib Terlecki tograph and the scanner? CIRCULATION DIRECTOR: Katherine Corvino CIRCULATION PROMOTION MANAGER: Joanne Guralnick Michael Burke FULFILLMENT AND DISTRIBUTION MANAGER: Rosa Davis New York City VICE PRESIDENT AND PUBLISHER: Bruce Brandfon ASSOCIATE PUBLISHER: Gail Delott TAYLOR REPLIES: The fractal character of a pattern does in fact reveal itself through SALES DEVELOPMENT MANAGER: David Tirpack SALES REPRESENTATIVES: Stephen Dudley, the way the number of filled squares changes with magnification. For something to be Hunter Millington, Stan Schmidt, Debra Silver fractal, the number of filled squares, N, must scale with the square length, L, accord- ASSOCIATE PUBLISHER, STRATEGIC PLANNING: Laura Salant ing to the power law relation N ∼ L–D. D is the fractal dimension—it quantifies the scal- PROMOTION MANAGER: Diane Schube ing relation among the patterns observed at different magnifications. This power law RESEARCH MANAGER: Aida Dadurian PROMOTION DESIGN MANAGER: Nancy Mongelli relation is true also for smooth Euclidean shapes. The distinguishing property is that

GENERAL MANAGER: Michael Florek for a smooth Euclidean line D = 1, whereas for a fractal line 1 < D < 2. BUSINESS MANAGER: Marie Maher Regarding the second point: as noted in the text, we examine the fractal behavior MANAGER, ADVERTISING ACCOUNTING AND COORDINATION: Constance Holmes over a range from about a meter down to a millimeter. For the fakes, the biggest distortion away from fractal behavior occurs at the small scales. After we established the frac- DIRECTOR, SPECIAL PROJECTS: Barth David Schwartz tal character of Pollock’s paintings, we then went back to the ﬁlm to determine the phys- MANAGING DIRECTOR, SCIENTIFICAMERICAN.COM: Mina C. Lux ical processes that created them. For large scales, the key was in the way that Pollock

DIRECTOR, ANCILLARY PRODUCTS: Diane McGarvey moved around the canvas (he actually followed motions called Levy ﬂights). At smaller PERMISSIONS MANAGER: Linda Hertz scales (10 centimeters and below), the ﬂuid dynamics become important: how the paint MANAGER OF CUSTOM PUBLISHING: Jeremy A. Abbate was launched from the brush, how it fell and how it seeped into the canvas. CHAIRMAN EMERITUS: John J. Hanley Fractals in the real world are different from mathematical fractals: they can’t go CHAIRMAN: Rolf Grisebach PRESIDENT AND CHIEF EXECUTIVE OFFICER: on forever. In fact, most fractals in nature continue over a magnification range of only Gretchen G. Teichgraeber about 20 times. Pollock is extraordinary in this regard, because his fractals are chart- VICE PRESIDENT AND MANAGING DIRECTOR, INTERNATIONAL: Charles McCullagh ed over a magnification of 1,000 times! His patterns are fractal down to the finest VICE PRESIDENT: Frances Newburg speck of paint, about one millimeter in size.

Finally, we use high-resolution images in 0.001 millisecond for a burst source at one act for “the good of the species”—a notion which distortion doesn’t occur until 0.8 mil- billion light-years observed between 100 and that has long been shown to be false. If one limeter. Also, before sending images through 300 keV; such small lags were undetectable can speak of a “goal” for individual or- the computer, we visually inspect them for by BATSE. Also, quantum gravity predicts that ganisms, it would be to maximize their ge- any distortions caused by bumpiness. higher-energy photons lag behind lower-ener- netic contribution to future generations. gy ones—contrary to the effect seen by BATSE. Don Luce LAGGING PHOTONS? The quantum gravity lags would be easi- Bell Museum of Natural History I read with interest the Profile of Fotini er to observe at GeV energies. We are excit- Minneapolis Markopoulou Kalamara [“Throwing Ein- edly awaiting the 2006 launch of the Gam- stein for a Loop”], by Amanda Gefter, and LEONARD REPLIES: I did not mean to imply the article “The Brightest Explosions in that organisms act for the good of the spe- the Universe,” by Neil Gehrels, Luigi Piro cies. It’s true that an individual’s motivation and Peter J. T. Leonard. I was particular- is to maximize its own reproductive success. ly intrigued by the following quotations. That said, from the long-term lens of evolu- From the Profile: “One experiment could tion (and the perspective of the population), be to track gamma-ray photons from bil- the act of individuals allocating energy to the lions of light-years away. If spacetime is next generation is what enables species to in fact discrete, then individual photons persist and succeed. should travel at slightly different speeds, depending on their wavelength.” From 3-D MEMORIES the article: “Roughly 90 of the [gamma- Memory is plastic, as Mark Alpert demon- ray] bursts seen by BATSE [the Burst and strates in Technicalities [“Getting Real”] Transient Source Experiment onboard when he recalls viewing the 1983 film the Compton Gamma Ray Observatory] Jaws 3-D through cardboard goggles form a distinct class of their own, defined GAMMA-RAY BURST produces intriguing photons. with red and blue filters. He’s describing by ultralow luminosities and long spec- the anaglyph process, which used one red tral lags, meaning that the high- and low- ma-ray Large Area Space Telescope (GLAST), filter and one green (or blue) one for 3-D energy gamma-ray pulses arrive several with the hope that it will detect such lags in viewing of projected monochrome images. seconds apart. No one knows why the gamma-ray bursts. The process used in Jaws 3-D, how- pulses are out of sync.” ever, was different; it permitted stereo- This may just be coincidence. I have YOU WIN SOME ... scopic projection in full color. It employs no idea what Markopoulou Kalamara’s I really enjoyed the “Scientific American polarizing filters at the projector and gog- theories suggest the arrival-time differ- 50.” A once-a-year summary of major gles with polarizing filters. I also remember ence should be for various wavelengths developments is a great way to get the big red and blue goggles from a series of 3-D of photons, and there must be myriad picture. Don’t change it (much) next year! Batman comic books in the early 1960s, possible explanations for the BATSE re- Mike Steiner however. Maybe the lenses Alpert results. But it struck me. via e-mail members were not from a movie at all. Jonathan Leete Tom Flynn Arlington, Va. As a longtime subscriber, I have never Buffalo, N.Y. seen so much space wasted as in the “Sci- GEHRELS AND LEONARD REPLY: The spec- entific American 50.” Surely you can find ALPERT REPLIES: You’re absolutely right. tral lags observed in gamma-ray bursts by better articles. I hope this won’t be an an- That’s what happens when you read too many BATSE are quite different from what is pre- nual waste. comic books. dicted by quantum gravity. The BATSE lags Peter Tiley observed between energies of 100 and 300 Dundas, Ontario ERRATUM In “On Thin Ice,” by Robert A. Bind- kilo-electron-volts (keV) ranged up to sever- schadler and Charles R. Bentley, a statement al seconds in length, with higher-energy pho- SECRETS OF SPECIES SUCCESS about global warming should have read: tons arriving before lower-energy ones. In “Food for Thought,” William Leonard “Around the world, temperatures have risen But quantum gravity predicts an effect on states that “the goal of all organisms is the gradually since the end of the last ice age, but the order of about three milliseconds per same: to devote sufficient funds to repro- the trend has accelerated markedly since the giga-electron-volt (GeV) per billion light-years duction to ensure the long-term success of mid-1900s”; we mistakenly printed “since

MARK A. GARLICK distance. This amounts to a lag of less than the species.” This implies that individuals the mid-1990s.”

The Wily Flu ■ Frozen Continent ■ Fishy Aviation

APRIL 1953 A MASSIVE SEARCH—“The elementary ber 2 two sledge parties were sent out. INFLUENZA VS. IMMUNITY—“The sero- particle corresponding to the gravita- The best record made was that of Capt. logical character of the A virus has tional ﬁeld has been named the graviton. Robert F. Scott, Dr. Edward Wilson, and changed seven or eight times since 1933, There can be little doubt that in a formal Lieut. Ernest Shackleton. These intrepid and each change in character has within mathematical sense the graviton exists. explorers traveled 94 miles to the south, a year been evident all over the earth. However, nobody has ever observed an reaching land in latitude 80 deg. 7 min. Soon after inﬂuenza A2 was found in the individual graviton. Because of the ex- This is the most southerly point yet at- U.S., it appeared in Australia and En- treme weakness of the gravitation inter- tained. The expedition proved a most se- gland as well. After it had taken hold, no action, in practice only large masses pro- vere test of the endurance of both men A1 strains were found anywhere. And so duce observable gravitational effects. In and animals. All the dogs perished, so for each successive change. It is a parasite the case of large masses, the number of that several men had to drag the sledges back. Lieut. Shackleton almost died from exposure.”

EASIER RIDER—“The increasing interest in motor bicycles manifested of late among cyclists is directly attributable to the numerous improvements which have brought various makes of these machines up to a high standard of excellence. The ‘Indian’ motocycle is one type of machine which has become quite popular in the cycling world. Great care has been exercised in the construction of the motor used in this machine, and by thorough testing under all conditions, it has been brought up to a high state of efficiency.” [Editors’ note: Before World War I, the Indian Motocycle Company was the largest manufacturer of motorcycles in the THE INDIAN motor bicycle, 1903 world.] APRIL 1853 whose only natural host is man. To sur- gravitons involved in the interaction is FLIES LIKE A FISH—“Theodore Poesche vive, it must pass continually from one very large, and the field behaves like a has presented a plan for navigating the human being to another—it is inhaled classical field. Consequently, many physi- atmosphere with a car propelled by a and lodges in the respiratory tract. But it cists believe that the individual graviton steam engine without employing a bal- soon finds itself in the position epidemi- never will be observed. Whether the loon. His plan is to build a long, narrow, ologists call ‘exhaustion of susceptible graviton has a real existence is one of the and light wooden vessel, with wings of hosts.’ In other words, almost the entire most important open questions in phys- canvas, and propel it by a screw propeller population becomes immune. This high- ics. —Freeman J. Dyson” driven by steam power. ‘My ship,’ he ly transmissible virus meets the situation says, ‘most nearly resembles the flying by a transformation of character—a mu- APRIL 1903 fish, which progresses by the spiral action tation that enables it to overcome its BRAVING ANTARCTICA—“Reports say the of the tail, while its extended fins support host’s immunity. —Sir Macfarlane Bur- ‘Discovery’ entered the ice pack Decem- it in the air.’ The screw propeller was net” [Editors’ note: Burnet was a co-win- ber 23, 1901, in latitude 67. On March proposed long ago to drive aerial ships ner of the 1960 Nobel Prize for Physiol- 24 the ship was frozen in, but the expe- with balloons, but could not do it then, ogy or Medicine “for discovery of ac- dition passed a comfortable winter near and to do so now without a balloon is an quired immunological tolerance.”] Mounts Erebus and Terror. On Septem- impossibility.”

s NASA investigates why Columbia repairing damage while in orbit. But if the ac- broke up during its reentry into the at- cident’s cause cannot be pinpointed or if a A mosphere on February 1, killing all major redesign of the three remaining shut- seven astronauts onboard, the space agency tles is required, NASA may have to accelerate faces some difficult choices. For more than a its development of a smaller, more reliable decade, aerospace experts had warned about spacecraft. the vulnerability of the aging, 100-ton space Previous efforts to replace the shuttle fleet shuttles to the superheated gases that envel- have been expensive failures [see “Has the op the craft as they descend to Earth. If in- Space Age Stalled?” by Mark Alpert; Scien- vestigators determine that a breach in Co- tific American, April 2002]. Last Novem- REENTRY TRAGEDY: lumbia’s heat shield or aluminum skin ber the agency committed $2.4 billion to pro- Fallen debris from the space doomed the mission, NASA might require ducing a design for an orbital space plane shuttle Columbia leans against a fence near Douglass, Tex. shuttle crews to inspect the craft’s exterior be- (OSP) that could ferry a crew of at least four fore reentry and perhaps devise a strategy for astronauts to the International Space Station. (With the shuttles grounded, NASA lost access to the station; only the Russian Soyuz and Progress spacecraft can ferry crews and sup- plies to the orbital outpost.) NASA’s plans, however, are still vague; the agency has not yet decided whether the OSP will be a winged vehicle like the shuttle, a lifting body (a squat craft shaped to maximize aerodynamic lift), or a capsule like Soyuz. And even if Congress approved an additional $10 billion to build the space plane, it would not be ready to carry crews into orbit until 2012. Dennis E. Smith, manager of the OSP program, is looking for

ways to speed up the schedule, but he cautions, AP Photo “I don’t think we can save a lot of time.” WILLIAM

The orbital space plane promises to be C much safer than the shuttle. The OSP would

hold only astronauts, not heavy cargo, so it DONNA M

22 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. news is that it could not perform all the shuttle’s tasks. NASA would have to develop an un- SCAN manned launch and docking system to send heavy payloads to the space station. And the OSP would have its own risks, of course. The safety record of even the most successful rock- ets is not perfect—the Delta 2, for example, has carried payloads into orbit 104 times since 1989 but did explode once, in 1997. FOUR DESIGNS for the orbital space plane (clockwise NASA would need to extensively test and up- from top left): lifting body; winged vehicle with sharp grade the boosters chosen to launch the OSP. leading edges; shuttlelike vehicle; and capsule, which To minimize the dangers of atmospheric may be the safest for reentry. reentry, the best design choice for the OSP A NEW VEHICLE may be a capsule shape. According to Theo- FOR ASTRONAUTS would be compact and light enough to be dore A. Postol, a space systems expert at the launched by a single-use commercial rocket Massachusetts Institute of Technology, a Boeing, Lockheed Martin, and a team consisting of Orbital Sciences such as the Delta 4. The shuttle, in contrast, blunt capsule falling through the atmosphere and Northrop Grumman have requires three rocket engines built into the ve- heats up much less than a winged vehicle already begun work on preliminary hicle, an external tank of liquid hydrogen and does. And by eliminating wings, wheels and designs for the orbital space plane. oxygen to feed those engines, and a pair of control surfaces, engineers could devote more The design proposed by Orbital solid-fuel boosters. of the craft’s mass to the all-important ther- Sciences is based on the HL-20 Lifting Body, a vehicle concept that The immense strain of a shuttle launch in- mal shield. After descending to the lower at- NASA studied in the early 1990s. vites hazards: a leak in a solid-fuel booster mosphere, the capsule could float on para- The space plane would be about 37 caused the loss of the shuttle Challenger in chutes to an ocean landing, just as the Apol- feet long (compared with 122 feet 1986, and a piece of foam insulation falling lo modules did in the 1960s. “Given all those for the shuttle) and have a from the external tank may have damaged benefits, is it really worth landing on a run- wingspan of about 35 feet (compared with 78 feet for the Columbia’s left wing shortly after its launch way?” Postol asks. shuttle). It could carry a crew of on January 16. The smaller size of the OSP NASA officials, though, do not seem en- five astronauts to and from the would also reduce the chance of a collision thusiastic about the capsule design. Smith, the International Space Station (the with micrometeoroids and man-made debris OSP manager, expresses concern about the shuttle typically carries seven). while the craft is in orbit. (Such debris could reliability of parachute mechanisms and Also, one of the space planes could be continuously docked to the have struck Columbia during its final mis- the cost of retrieving the spacecraft from the station in case it is needed for sion.) And the OSP’s heat shield could be ocean. Postol thinks a different factor may emergency evacuation. fashioned from newly developed metallic explain the agency’s reluctance: “I expect that An editor’s commentary about the panels, making it more resilient than the shut- NASA will resist the capsule for emotional odds against Columbia appears at tle’s patchwork of ceramic tiles. reasons. The astronauts want to fly the vehi- www.sciam.com, under the

NASA ARTIST CONCEPT The main disadvantage of the space plane cle.” Even if that makes for a riskier reentry. “Explore” link.

ENVIRONMENT Oiling Up Spain A SUNKEN TANKER COULD TARNISH SPAIN FOR DECADES BY LUIS MIGUEL ARIZA

housands of tons of heavy fuel remain toxic fuel have oozed from 20 cracks in the in the bow and stern sections of the hulls as semisolid black strings, like tooth- T Prestige, the oil tanker that split in half paste being squeezed from a tube, and have off the northwestern coast of Spain on No- drifted toward the sea surface. It has become vember 19, 2002. It sank to the seabed, more Spain’s worst ecological disaster ever, halting than 3,500 meters deep in the Atlantic Ocean coastal ﬁshing and polluting beaches. The some 200 kilometers from Galicia. Tons of ship has already spilled at least 30,000 tons

www.sciam.com SCIENTIFIC AMERICAN 23 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. news SCAN of oil, and researchers aren’t sure when the means, he says, that the leakage won’t stop. seepage will stop. Many sunken ships have leaked signifi- At first, scientists thought that the fuel cant amounts of oil decades after their wreck- would freeze: oil remains fluid to six degrees age, according to the National Oceanic and Celsius, and the deep water around the wreck Atmospheric Administration. The SS Jacob is at 2.75 degrees C. Experts guess that the Luckenbach, a freighter that sank in 1953 off Prestige left port from Ventspils, Latvia, in the the coast of San Francisco, caused periodic Baltic Sea with 77,000 tons at 50 degrees C. “mystery spills” in the Bay Area until it was But no one knows what the oil temperature is identified and much of its oil removed just now. According to Malcolm L. Spaulding, last year. The oil tanker Nakhodka, which professor of ocean engineering at the Univer- sank in 1997 to a depth of 2,500 meters near sity of Rhode Island, the calculations of the the Japanese island of Honshu, continues to cooling time for the oil in the bow and the seep small quantities of fuel, Girin says. stern, which lie 2.5 kilometers apart on the To prevent any more oil from the Prestige seafloor, have proved extraordinarily difficult. from reaching Spain’s coast, a commission of In principle, the fuel in contact with the external walls of the hulls should cool faster than that in the center of the tank. The time it takes for all the oil to cool down depends on the amount and rate of mixing, a critical TOO SLICK factor “that complicates TO HANDLE? heat transfer from the oil to the tank walls and fi- Researchers have proposed nally to the seawater,” several ways to deal with the Spaulding explains. If the remaining oil in the Prestige, none oil mixed together well, of which is ideal. Entombing the wreckage with concrete, sand or the entire cargo should plastic would be difficult to do have cooled off and fro- underwater. Exploding the hulls zen in 40 days. That did IGNOMINIOUS END to the Prestige, carrying 77,000 tons of fuel oil, as it broke and successfully retrieving the not happen, Spaulding rein half off the coast of Spain in November 2002 and sank to a depth of freed oil at the surface with ship- marks, probably because 3,500 meters. Its cargo could contaminate the environment for decades. mounted skimmers depend strongly on weather conditions; the mixing is substantially rough seas could lead to reduced. He now anticipates “cooling times Spanish scientists used the French submersible uncontrolled spreading. of many months to several years.” Nautile to patch the cracks. This past Janu- The best bet may be direct Michel Girin, director of the French Cen- ary the Nautile blocked 17 of the 20 ruptures pumping of the fuel. Smit, the ter of Documentation, Research and Experi- with steel plates or bell-shaped caps, slowing Dutch salvage company that mentation on Accidental Water Pollution, down the leakage rate of 120 tons a day soon raised the Russian submarine notes that because the viscous fuel that es- after the sinking to a couple tons by mid-Feb- Kursk, engineered a system that retrieved the oil from two tankers capes from the cracks probably does not ruary. Emilio Lora Tamayo, head of the com- lying 80 meters underwater near come from the ship’s middle, the Prestige will mission, admits that the patches will not last Bussan, Korea. “Basically, we go effectively be a “permanent source of pollu- forever and will need continual maintenance. down with little robots that drill tion.” Simulations in a pressure chamber that Even a complete sealing would be a tempo- holes in the tank,” explains Lars mimics the conditions at the tanker (about 100 rary solution: researchers calculate that the Walder, a Smit spokesperson. “By atmospheres) have revealed that the fuel will hulls of the tanker will erode and break apart mixing the oil with hot water or a Corbis special type of seed oil, we can never solidify. “We have seen that even at within 23 to 40 years. The neutralization of make the fuel more fluid in order to –10 degrees Celsius, it continues to flow,” re- the Prestige, Tamayo observes, “is a techno- be able to pump it out.” The marks Jean Croquette of the French Research logical challenge never attempted before.” company admits, however, that the Institute for Exploitation of the Sea. “The technology to work at depths in excess of 2,000 meters has yet density of the fuel is lower than that of the sea- Luis Miguel Ariza is a science writer

to be developed. water, so it retains the capacity to ﬂow.” That based in Barcelona, Spain. REUTERS NEWMEDIA, INC.

ith its often telltale stench of rotten eggs, sulfur would not top most peo- W ple’s list of favorite culinary season- ings, but plenty of bacteria adore it. What’s more, their predictable preferences for certain flavors of sulfur can be preserved inside rocks for billions of years, revealing detailed stories about the earth’s distant past—most recently, a scenario for why the planet didn’t freeze when the sun was considerably cooler. It all boils down to who’s eating what. All organisms are finicky, and the sulfur-loving bacteria are no exception. They prefer sulfur 32, the element’s lightest isotope, to heavier sulfur 34 when given the choice. In the modern world, they leave a waste product (usually recorded in the mineral pyrite) with a surplus of sulfur 32 that is as much as 7 percent greater than that of their food source, a sul- many times the heat-trapping capacity of car- WEALTH OF SULFUR feeds a prolific fur compound called sulfate (today a com- bon dioxide—may have been more abun- suite of bacteria on earth today, mon salt in seawater). But the surplus of sul- dant, in part because it could stick around but its scarcity in the ancient ocean kept the microbes at bay. The fur 32 in pyrite that formed before 2.5 billion a whopping 10,000 years in the oxygen-poor mound shown, in Wilmington, Calif., years ago rarely exceeds 1 percent. This dis- atmosphere of the past. But what generated is a stockpile of refined sulfur. crepancy suggests to geochemists that back the continuous supply of the gas was still then, during a geologic eon known as the uncertain. GEMSTONE Archean, sulfate was scarce: with less food That’s where the sulfur lovers reenter available, sulfur lovers couldn’t afford to be the story. Habicht’s team calculated that their GOSSIP as picky about the isotope they favored. sulfate-starved bacteria would perform their Who would have thought that a Indeed, when Kirsten S. Habicht of the daily chores, such as decomposing the remains girl’s best friend could whisper University of Southern Denmark in Odense of other organisms, much more slowly—at tales of an ancient earth choking and her colleagues grew cultures of three rates 30 to 90 percent lower than those fed a from a lack of oxygen? James Farquhar of the University of kinds of modern sulfur-craving bacteria, they modern serving of sulfate. In the ancient Maryland and his colleagues found that the sulfur 32 surplus dropped to world, that would have left countless open recently found that tiny specks of the low value recorded in Archean rocks only seats at the dinner table for another set of hun- iron sulfide inside African when the researchers reduced sulfate concen- gry microorganisms, the methanogens. A pro- diamonds bear a bizarre ratio of trations below 200 micromolar—not even liferation of these methane producers could sulfur isotopes that results only 1 when ultraviolet radiation from the ⁄ 100 the amount present in oceans now. have sustained a strong greenhouse effect. sun breaks apart sulfur-rich gases Such low levels of sulfate indicate that the Uwe H. Wiechert of ETH Zentrum in in the atmosphere. Farquhar had Archean atmosphere was virtually devoid of Zürich says that the calculations of Habicht’s shown previously that this oxygen. Without oxygen to help wear down team are the first clear suggestion that meth- atmospheric breakup diminishes the continents, sulfur minerals stay locked in anogens provided that needed greenhouse-gas dramatically once oxygen builds up in the atmosphere and the ozone the rocks and unavailable to hungry bacteria. supply. But to know for sure will require in- layer begins blocking the radiation. Extremely low sulfate levels could also ex- dependent verification of methane’s behavior The diamond discovery further plain why the oceans did not freeze, consid- in the Archean atmosphere, which might have implies that this unique sulfur ering that the sun was about 25 percent dim- resembled present-day conditions on Saturn’s signature can survive a geologic mer. Scientists have long believed that green- methane-shrouded moon, Titan—the target roller coaster: riding from the atmosphere to deep within house gases must have been insulating the for NASA’s Huygens probe in 2005. In the the earth’s mantle, where earth much more efficiently than they do to- meantime, stinky sulfur will undoubtedly re- diamonds form, and then back to

CORBIS day. They have argued that methane—with veal more sweet secrets. the planet’s surface.

he hardest thing to prove is something ten 10 times more precise. So Kopeikin and you think you already know. How can Fomalont went one step further: to look not T you be sure that you’re proving it, rather only for the bending caused by a static body than merely reasserting your belief? So it is but also for relativistic effects caused by the with the latest test of Einstein’s general theory motion of that body. Such effects depend on of relativity—a mea- the ratio of the body’s velocity to c. For Jupi- Apparent motion surement of the speed ter, which orbits the sun at 13 kilometers a of quasar at which changes in a second, the ratio is about one part in 20,000. gravitational field prop- That seems awfully small, but the researchers Actual position agate. If the sun sud- calculated that geometric factors would mag- of quasar denly shattered into nify any effects to detectable levels. a million pieces, this Last September they put their plan into ac- speed would determine tion when Jupiter passed close to the line of how many minutes sight between Earth and a quasar. The quasar of blissful ignorance image scooted 1,300 microarcseconds across EARTH the denizens of Earth the sky—with a 50-microarcsecond skew, just would have until our as expected from relativistic effects. orbit went haywire. In So far, so uncontroversial. The fun begins JUPITER Einstein’s theory, the when you ask which relativistic effect was op- speed of gravity (ab- erating. There are oodles of possibilities, and LIKE A LENS, Jupiter bends the breviated cg) exactly equals the speed of light Einstein’s notoriously subtle equations do not light rays from a distant quasar. in a vacuum (c). specify which mathematical term corresponds The yellow ray is unaffected by Lo and behold, that is what a physicist- to which physical effect. Kopeikin and Foma- Jupiter and takes a direct path to Earth; the dotted lines show the astronomer duo announced at the American lont contend that the dominant effect was the illusory paths of the ray. Jupiter’s Astronomical Society meeting in January. Ein- propagation of gravity. As Jupiter travels, its motion causes the quasar image to stein, they concluded, was right once again. gravitational force on the ray varies, and the trace out a circle. Relativistic Yet most relativity researchers are skeptical. variation takes a little while to travel through effects skew the circle (not shown). “It’s a beautiful experiment that gives a very space to the ray. To isolate this effect, the sci- nice new confirmation of general relativity, entists constructed an alternative version of EINSTEIN VERSUS but it’s still unclear whether it’s testing the relativity, in which cg could differ from c. NEWTON speed of gravity,” says Steven Carlip of the They were then able to infer a value for cg University of California at Davis. from the data, without presuming it. The two In Newton’s theory of gravity, the No one questions the basic experimental c’s turned out to have the same numerical val- speed of gravity (cg) is infinite; if the sun blew up, Earth’s orbit would setup, devised by Sergei Kopeikin of the Uni- ue, with a precision of 20 percent. change instantaneously. But versity of Missouri and Edward Fomalont of But others, notably Clifford M. Will of Einstein’s special theory of the National Radio Astronomy Observatory. Washington University, take a different ap- relativity wouldn’t look too kindly The idea was to look for the effect that a near- proach to extending relativity and attribute on that. To preserve the distinction between cause and effect, the by celestial body has on the light rays from a the observed skew to the better-known rela- speed of light (c) must be the more distant object. The nearby body should tivistic effects of time dilation and length con- ultimate speed limit. Special bend the light rays, temporarily shifting the traction. From the vantage point of Earth, Ju- relativity also suggests that cg image of the distant object. In a famous (if piter’s moving gravitational field looks slight- cannot be less than c: if it were, controversial) expedition in 1919, English as- ly flattened, which alters the amount of light gravity would behave differently for different observers. tronomer Arthur Eddington detected the de- deflection that we perceive. This flattening de- Unfortunately, Newton’s theory of flection of starlight by the sun. Just over a pends on c but not on cg. The propagation gravity cannot accommodate a decade ago high-precision radio astronomy— of Jupiter’s gravity does play a role, but Will finite cg without making orbits in particular, very long baseline interferome- argues that it corresponds to a different (and unstable. The conflict between try, which links together far-flung radio dish- much smaller) term in the equations. If so, Newton’s theory and special relativity led Einstein to devise an es into a single globe-spanning telescope—saw Kopeikin and Fomalont cannot infer a value entirely new theory of gravity, the minute bending caused by Jupiter. for cg.

general relativity. Since then, radio interferometry has got- The disagreement will not be easy to SLIM FILMS

28 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. news resolve. Most researchers lean toward Will’s probing something unique. Sorting things out approach, which builds in consistency with will take more theoretical work as well as di- SCAN other experimental tests. Some go so far as to rect measurement of gravitational radiation. say that the entire debate is pointless, because No mainstream physicist doubts that cg equals there are tests that have higher precision, but c. But in science, it is not enough to be right. others think Kopeikin and Fomalont could be You have to be right for the right reasons.

WILDLIFE Out of the Woods MOVING THE GRAY WOLF OFF THE ENDANGERED LIST BY EMILY HARRISON

nly six domestic animal species have where it was formerly an important predator ever earned their way off the U.S. En- in that ecosystem. They also argue that out O dangered Species List. The gray wolf is West the population is too thin for the wolves closing in on becoming the seventh. Although to set out from the recovery zones and into many wolf biologists back the decision, not their former ranges in the southern Rockies all wildlife advocates are cheering the pend- and the Paciﬁc Northwest. ing status change. In 1974, after a century of aggressive ex- termination efforts had nearly extinguished WATCHING gray wolves in the lower 48 states, the En- THE WOLF dangered Species Act took effect, and the Delisting the gray wolf does not dwindling species was whisked onto the list. mean that it will be left to its own The U.S. Fish and Wildlife Service (FWS) sub- devices. The U.S. Fish and Wildlife sequently initiated recovery programs for the Service must monitor the wolf gray wolf in three regions, setting population populations in the delisted areas for at least five years and can goals for the West, East and Southwest. “emergency relist” the species if With federal protection and reintroduc- necessary. The FWS also requires tion programs to seed the West with ecologi- that all key states within a cally appropriate wolves from Canada, gray recovery zone submit biologically wolf populations burgeoned. Today there are acceptable wolf management plans before the species is 44 breeding pairs (a total of 664 wolves) in removed from the list. The plans the Western zone, exceeding the target of 30. deal with issues such as In the Eastern area, over 3,800 wolves live in population control, compensation the Great Lakes region—almost triple the tar- for loss of livestock, recreational hunting, and permission to defend get number—and a new population of over property. “There’s no requirement 600 wolves teems in the states around Min- for state management plans in the nesota. (In the Southwest, recovery of the Endangered Species Act,” Mexican gray wolf is still in its infancy, and the TWO SIDES: Gray wolf supporters disagree about the comments Midwest recovery animal’s endangered status will remain intact.) next steps in the species’ recovery. coordinator Ron Refsnider. “We’re Because the wolf populations have now imposing that because of the wolf’s unique situation.” met their goals for the West and East, the FWS FWS biologists respond that their job is to wants to reclassify the wolf from endangered ensure that the wolf is no longer in danger of U.S. species removed from the to threatened and delist the species in all states extinction, not to restore the species to every Endangered Species List: outside its historical range. The FWS fully ex- place it could live. “The Endangered Species Brown pelican, 1985 pects the reclassiﬁcation proposal to pass this List is not a tool for other agendas. The act American alligator, 1987

Corbis spring and hopes to delist the populations in mandates that if a species doesn’t need pro- Arctic peregrine falcon, 1994 the Northwest and Midwest in the next year. tection anymore, you must remove it,” insists Several wildlife groups, however, protest Ed Bangs, wolf recovery coordinator for the Gray whale, 1994 that the proposed status change is premature. West. L. David Mech, wolf expert and senior American peregrine falcon, 1999

W. PERRY CONWAY The wolf has not returned to the Northeast, research scientist with the U.S. Geological Aleutian Canada goose, 2001

www.sciam.com SCIENTIFIC AMERICAN 29 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. news Survey, agrees that the gray wolf is no longer terminated. Because deep-seated animosities SCAN at risk of extinction in the lower 48 states. against the wolf still exist, wolves face ﬁercer “When recovery goals were planned, certain threats than other recovered species. numbers were set that would signify recovery. Despite some persisting hostility toward I see no evidence that those numbers were too the gray wolf, experts assert that the situation low.” Mech believes the genetic diversity and is not the same as it was before 1974. Atti- population growth rate in these numbers are tudes have grown more tempered with public sufﬁcient for maintaining viable populations. education, which Mech expects will continue Even so, opponents of the change contend to serve the animal: “We started off 20 years that the wolf is unique among recovered spe- ago saying, ‘Save the wolf.’ We’ve done that. cies: it is the only one that was deliberately ex- Now the thing to say is, ‘Manage the wolf.’”

CLONING Ma’s Eyes, Not Her Ways CLONES CAN VARY IN BEHAVIORAL—AND PHYSICAL—TRAITS BY CAROL EZZELL

ne pig savors a ripe banana, whereas its The pigs are just the latest evidence that cloned sister turns up its snout. Anoth- clones aren’t mere duplicates. The world’s ﬁrst O er always thrashes its trotters to get cloned cat, Cc (for “carbon copy”), is no copy- away when it is picked up, whereas the others cat, according to her creators, Duane C. Krae- CLONED CAT Cc gets a nuzzle in the nuzzle into a human embrace. Although mer and his co-workers, who are also at Texas ear from her genetic twin. clones have been described as identical twins, A&M. Cc is more curious and playful than studies of the behavioral—and even physi- Rainbow, the cat from which she was cloned. cal—traits of cloned animals are showing that Their coats are also different (although that that is not necessarily the case. may have more to do with the way calico coats Ted Friend and Greg Archer of Texas are inherited—a calico’s spots result from the A&M University created the cloned piglets. random migration of pigment-carrying cells They observed as much physical and behav- during development). ioral variation among the members of two lit- Robert P. Lanza of Advanced Cell Tech- ters of cloned pigs (of four and ﬁve individu- nology in Worcester, Mass., says it should als, respectively) as among those of two litters come as no surprise that clones are not exact of eight pigs bred naturally. Not only did the replicas, because among humans, identical cloned siblings show distinct food preferences twins often have strikingly varying personal- and temperaments, but they also varied in ities. He and his colleagues have observed the physical characteristics: some had more bristly same phenomenon among their herds of IN MEMORIAM: coats or fewer teeth than others did. cloned cattle. Far from behaving similarly, GOOD-BYE, DOLLY The clones are “just like normal pigs,” herds cloned from the same individual devel- Friend concludes. “They’re not at all like iden- op the usual social hierarchy, with some cows The world’s first cloned sheep, tical twins.” Conditions in the uterus could being more skittish and others more bold. Dolly, is destined for permanent display at the National Museum of play a role, he speculates. The two cloned lit- Lanza suggests, though, that cloning might Scotland—after her date with a ters were borne by different surrogate sows, enable scientists to study the importance of taxidermist. Dolly was euthanized and the dissimilarities are even more pro- genetics in behavior. His group collaborated in February at the age of six, nounced between the litters. with a team at Wake Forest University two roughly half the average life span The poorly understood phenomena called years ago to attempt to clone an alcoholic of a normal sheep. She was suffering from a lung infection that epigenetics also has an effect. Each individual monkey named Buttercup. Their objective usually afflicts newborn cloned carries two copies of a given gene. In certain was to determine whether the cloned offspring animals as well as from chronic instances, one copy is turned off if it is inherit- of an alcoholic animal would also become ad- arthritis, another seemingly ed from the mother, whereas other genes have dicted to alcohol and to examine the degree to

common affliction of clones. Her the paternal copy silenced. Researchers are which alcoholism has a genetic basis. The AP Photo poor health—and now death—has fueled debates over the safety of now trying to ﬁgure out what determines such cloning attempt failed, but such studies might cloning and the ethics of using the selective gene expression and how the pattern one day allow researchers to probe more pre-

technology to create human babies. is established in the developing embryo. cisely the inﬂuence of genes on behavior. PAT SULLIVAN

he poverty threshold—the level of in- Bureau of Labor Statistics and her colleagues, come that separates the poor from the builds on the more extensive statistics now T not poor—was the brainchild of econo- available. The results, depicted by the purple mist Mollie Orshanksy of the Social Security line in the chart, yield an improved threshold, Administration, who developed it in the ear- 55 percent higher than the official level. ly 1960s. Orshanksy did not have the exten- Another approach is to base the threshold sive data on the income and consumption on purely subjective perceptions. In 1992 the habits of Americans needed to fashion a com- Gallup Organization asked Americans, “What pletely satisfactory formula; as a result, it had is the smallest amount of money a family ... certain built-in inequities, such as an under- needs each week to get along in this commu- estimation of the cost of nonfood items. nity?” The average of their answers is the ba- After a time other problems became ap- sis of the subjective threshold calculation, in- parent. The formula did not allow for chang- dicated by the dark blue line. On average the ing demographics, including the substantial respondents named a figure 76 percent high- rise in the number of working mothers, er than the official poverty level. whose costs for child care were not factored Still another method focuses on assets into the formula. Nor did it take into account rather than income. Economists Asena Caner higher Social Security payroll and other tax- of the Jerome Levy Economics Institute at es levied on the working poor. Nor did it ad- Bard College and Edward N. Wolff of New just for geographic variations in the cost of York University have calculated several mea- living, such as the two-to-one differential be- sures of asset poverty. In one, indicated by the tween San Francisco and Houston. The only green line, they define asset poverty as a net significant adjustment made was for cost-of- worth insufficient to cover minimal living ex- living increases. penses for three months. In a similar measure, To remedy these and other shortcomings, indicated by the light blue line, they define the MORE TO economists tried to devise a better formula. term as insufficient liquid wealth to cover these One, constructed by Thesia I. Garner of the expenses. (Liquid wealth is cash and other EXPLORE 50 easily monetized assets.) Under the latter def- Measuring Poverty: A New inition, a significant proportion of middle- Approach. Edited by Constance F. Asset poverty 45 class people would be considered at risk for Citro and Robert T. Michael. threshold National Academy Press, 1995. (liquid wealth) poverty. Both the asset poverty lines show a 40 different trend than the income poverty lines, Experimental Poverty possibly because of changes in savings rates 35 Measurement for the 1990s. over time. Thesia I. Garner et al. in Monthly Asset poverty Labor Review, Vol. 121, No. 3; 30 threshold The official threshold data were highly useful in the 1960s, but now they are outdat- March 1998. (http://stats.bls. (net worth) gov/opub/ml/mlrhome.htm) 25 Subjective ed and, according to some, greatly understate threshold the problem. Since at least 1995, when a pan- 20 Asset Poverty in the United “Improved” el of experts under the aegis of the National States, 1984–1999: Evidence threshold from the Panel Study of Income 15 Research Council recommended new guide- below Various Poverty Thresholds (percent) Thresholds Poverty Various below lines, a growing consensus has emerged that Dynamics. Asena Caner and Edward N. Wolff. Levy 10 Official poverty the official measure is inadequate. Most econ- threshold Economics Institute, Working omists argue that it should be discontinued Paper No. 356; 2002. 5 and replaced by a revised measure or perhaps (www.levy.org) U.S. Population 0 even several measures, including at least one indicator of asset poverty. United States Poverty Studies 1980 1985 1990 1995 2000 2005 and Poverty Measurement: The Year Past Twenty-Five Years. Howard SOURCES: U.S. Census Bureau; Thesia I. Garner et al.; Rodger Doyle can be reached at Glennerster in Social Services

RODGER DOYLE Asena Caner and Edward N. Wolff; Gallup Organization [email protected] Review, Vol. 76, No. 1; March 2002.

The hard part of constructing superdense computer chips isn’t crowding bits onto a silicon wafer; it’s reading each individual magnetic state, 0 or 1. The smaller the bit, the weaker its magnetic field. Now Susan Hua and Harsh Deep Chopra of the State University of New York at Buffalo describe a device whose electrical resistance changes by 100,000 times in a magnetic field—in principle, sensitive enough by far to read terabit-dense bits (1,000 times denser than bits on current chips). The device, a nanoscale nickel “whisker,” relies on an effect called ballistic magnetoresistance (BMR). In BMR, an applied magnetic field causes electrons to shoot through a wire with little ricocheting off atoms. Key to the effect were pinch points that result from the whisker’s manufacture and seem to make electrons go ballistic. The team reports in the February Physical Review B that it can reliably craft such structures. Chopra adds that BMR devices could also make useful biological sensors. —JR Minkel

PHYSICS Skipping for Smarties DATA POINTS: INVADED NATION An inquisitive seven-year-old son has led a physicist to lay out the science behind stone skipping, a.k.a. Life in a new country can be a lot smutting, skiffing, ricochet, or “ducks and drakes.” Ly- easier. Two studies, which examined 473 European plant deric Bocquet of the University of Claude Bernard species and 26 animal species Lyon in France reduced the problem to its essentials: that have invaded the U.S., confirm a thin, flat stone rebounding off a uniform surface of long-standing thinking that such water at a shallow angle, like a water ski skimming species tend to have fewer over a lake. By formulating equations of motion for the enemies and infections in their new digs. They are therefore better stone, Bocquet found that its initial speed and espe- able to survive and to crowd out cially its rate of spin are key to achieving that satisfy- indigenous flora and fauna. ing string of splashes. Giving the stone an initial spin Invasive species are considered generates a gyroscopic effect that minimizes tilting af- the second biggest threat ter each impact. If the stone goes too vertical, it sinks. to biodiversity, after habitat destruction. According to his equations, the world record for skips, 38, corresponds to a stone flying 12 meters and whirl- Percent drop in fungal infections SKIP THIS: The physics of a stone’s throw. ing 14 times a second. The work appears in the Feb- among European plants after ruary American Journal of Physics. —JR Minkel invading the U.S.: 84 Percent drop in viral infections: 24 Percent drop in all diseases: 77 MOLECULAR BIOLOGY Average number of parasites on a species in its indigenous range: 16 Number of parasites that Motoring with RNA accompany an invader and you have more than a spoonful of alphabet soup—you have to its new range: 3 Put RNA and ATP together, one of the strongest nanometer-size motors and what may have been a crucial step in the ori- Number the invader subsequently picks up: 4 gin of life. For decades, scientists knew that RNA ferried information in cells and could help catalyze reactions. Such a central role suggested that RNA existed as the underpinning for DNA Number of nonindigenous species in the U.S.: at least 30,000 and proteins. Now molecular virologists at Purdue University have found that in the bacte- Annual cost of damage done by ria-killing virus Phi 29, ATP can bind to and fuel a remarkably powerful motor made of six ILLUSTRATION BY MATT COLLINS these species: $123 billion RNA molecules. The virus subsequently relies on this ATP-powered RNA to shuffle its genes. The ability to bind to ATP was once thought to be limited to proteins. The researchers sug- Corbis; SOURCES: Nature, February 6, 2003; economic costs from a gest that RNA not only seeded life but also could have directed how ATP was used. They hope January 1999 report by David to devise machines that fuel themselves with organic molecules. The findings appear in the Feb- Pimentel of Cornell University and

his colleagues. ruary Journal of Biological Chemistry. —Charles Choi CHRIS VINCENT

The much anticipated Wilkinson Microwave gular scales, which might mean the universe Anisotropy Probe (WMAP), recently named is finite in size with a strange topology. The for the late Princeton University astrophysi- main WMAP paper is available at arXiv.org/ cist David Wilkinson, has observed the cos- abs/astro-ph/0302207. —George Musser mic microwave background radiation with about 30 times the resolution of NASA’s earlier COBE mission. Besides bearing out prevailing paradigms and nailing down key parameters, WMAP has delved into a whole new level of physics. Polarization of the radiation, never before measured with such precision, provides novel evidence for the theory of cosmological inflation and reveals when intergalactic gas became ionized (presumably by the very first stars). Combined with other data, WMAP finds a relative dearth of small BRIEF spots in the radiation, a phenomenon known POINTS as tilt. Not only does that winnow out certain ■ Food for thought: recent models of inflation, it could solve a nagging UNIVERSE AT AGE 380,000 YEARS was seen by the increases in American crop mystery: why the universe has fewer small COBE satellite a decade ago (top) and recently by the yields may have stemmed from galaxies than models predict. Finally, WMAP sharper-eyed WMAP satellite (bottom). Yellows and short-term climate changes reds are warmer (hence, denser) regions; blues are confirms a puzzling discrepancy noted by rather than farm management cooler (sparser). practices such as crop COBE: a lack of features on the largest an- diversification, pesticide spraying and fertilizer use. Science, February 14, 2003 PLANT GENETICS ■ After dropping out in 1998, the U.S. will rejoin the $5-billion Another Chance at Life International Thermonuclear Experimental Reactor (ITER), Reliving the teenage years may not be possible, but plants actually can get a second chance an attempt to create self- at growing up. Newborn sprouts just out from their seeds can suspend growth for up to 30 sustaining fusion by 2014. days if their environs turn risky, such as during Indian summers, in winter or in untimely U.S. Department of Energy press droughts. Plant molecular biologists at the Rockefeller University investigating the weed Ara- release, January 30, 2003 ) bidopsis thaliana have found a protein that is involved in granting plants this new lease on life. ■ A new kind of solar cell, in which bottom This compound, named AFP, restores arrested development by binding to another protein

. ( a dye on a metal surface absorbs called ABI5, which the researchers previously discovered stalled the growth. “ABI5 and AFP light and produces electricity, are kind of like yin and yang,” says Luis Lopez-Molina, one of the protein’s discoverers. Fur- has a surprisingly high ther studies to locate molecules that promote one protein or the other could help crops resist efficiency. Its constituent drought or save otherwise wasted seeds that sprout premature- materials are cheaper and more durable than conventional ly. The work appears in the February 1 Genes & Development. photovoltaic sources, such Photo Researchers, Inc —Charles Choi as silicon. Nature, February 6, 2003

); J. BURGESS ■ Pure oxygen helps to repair top wounds that resist healing with sutures, creams and other standard treatments. The oxygen was kept in contact with the skin via an adhesive-edged plastic wrap and applied for GERMINATION relies on 90 minutes a day. yin-and-yang proteins.

NASA/WMAP SCIENCE TEAM ( Pathophysiology, January 2003

Working Weeds A German company develops a way to peek into plant metabolism By KATHRYN BROWN

Herbicide chemistry may not sound particularly in- derstood: like people, plants take in nutrients (sun, wa- spiring. But in 1995, when Richard N. Trethewey heard ter and air) and then metabolize, or transform, those nu- a talk on how herbicides affect the metabolism of bar- trients into lots of other things (metabolites), from vi- ley, he was struck by an idea. At the time, the chemi- tamins to defense toxins. But how does this chemical cal company BASF was using gas chromatography to choreography play out? characterize the metabolic effects of potential herbi- That was largely a mystery. And although the cides. Could this technique, Trethewey wondered, be emerging field of functional genomics had just begun to expanded to profile everyday metabolism in plants? link genes to their protein products, most techniques Like many, Trethewey, then a biochemist at the stopped short of defining metabolic pathways. In con- Max Planck Institute of Molecular Plant Physiology in trast, metabolic profiling—or tallying a plant’s metabo- Golm, Germany, had hopes of engineering plants to lites, after altering its genes—seemed capable of cap- grow in different environments, grow new drugs or sim- turing information about those pathways more quick- ply grow better. The notion of metabolism was well un- ly. Done systematically, profiling might identify how genes regulate a metabolic process and screen for those with desirable traits. After some preliminary experiments with transgenic potatoes, Trethewey was convinced that the method could work. He and five colleagues drafted a business plan, sent it to venture capitalists and biotech companies, and finally struck a deal with BASF, which promised them $26 million over five years to develop the idea into a viable product. In 1998 the team founded the Berlin-based firm Metanomics (“metabolism” combined with “genomics”), which aims to identify key plant metabolism genes—for instance, those that allow plants to tolerate cold or generate extra oil—and then license its novel plant collection and genomics database to breeders and biotech firms. To do so, the company has built a broad technology platform, from genetically modifying plants to growing, testing and cataloguing them in its MetaMap database. The endeavor involves 90 staff members, 50 mass spectrometers, 4,500 square meters of labs, offices, greenhouses and growth chambers, and more than 140,000 plant lines. At Metanomics, the hunt for major metabolites is straightforward, if exhausting. The company has fo- MODEL PLANT: The weed Arabidopsis thaliana has cused early efforts on the weed Arabidopsis thaliana, helped Metanomics reveal key pathways that could let plants tolerate cold or generate extra oil. the first plant to have its genome fully sequenced. By

packaging a gene silencer into an agrobacterium, which METANOMICS

34 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. then infects Arabidopsis seeds, scientists are engineering a random, “knockout” group of plant lines, each missing the activity of just one gene or DNA segment usually found in Arabidopsis. Using a similar technique, the staff is introducing novel genes from yeast and other organisms to create an “overexpression” group of plant lines, each bearing one additional gene. After being bred for two generations, modified plants go head to head in tests with unmodified plants, which serve as controls. Researchers feed ground-up plant tissue to mass spectrometers, which use gas or liquid chromatography to dissolve and separate the metabolites inside. Those metabolites then get chopped into ion fragments and sorted by size. After all this is done, scientists know which metabolites each plant had and in what amounts. If a plant leaf brims with a food oil, for instance, Metanomics can detect that change—and backtrack to the responsible gene. So far the company has bred more than 40,000 knockout and 100,000 overexpression plant lines. Typical of functional genomics, metabolic profiling involves genetically altering organisms and then rapidly screening them for chemical or physical changes. What is unique is the focus: these profil- ers seek a snapshot of a plant’s complex metabolome, or network of metabolic pathways. Like factory inspectors, they want to know precisely how plants churn out chemical products. Metanomics, for instance, hopes to learn which stress-tol- erant pathways help plants to survive the cruel outdoors. So the company exposes both genetically modified and unmodified plants to extreme conditions, depriving them of water or light, for example. Sci- entists note individual plant responses in the MetaMap database—and then use bioinformatics software to look for biochemical patterns in those responses. How do unmodified plants usually respond to chilly temperatures? Which modified plants do better—and how do www.sciam.com SCIENTIFIC AMERICAN 35 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. Innovations

they differ metabolically? Or, as Trethewey puts it: has identified the functions of roughly 300 novel plant “Which of Arabidopsis’s 27,000 genes are really im- genes and intends to publish early results soon. The portant for influencing these metabolic networks, these MetaMap database will also become available to cus- stress functions? That’s a clear goal, where we will be tomers later this year. Metanomics is not disclosing any able to make substantial progress.” precise finds, although the discoveries include some The numbers are substantial. During an average stress-tolerance and amino acid synthesis genes. week, Metanomics generates about 150 cloned and Richard A. Dixon, director of plant biology at the transformed plant genes, 10,000 chromatographic and Samuel Roberts Noble Foundation, a nonprofit organi- mass-spectrometric measurements, and 150 gigabytes of zation in Ardmore, Okla., that works to improve plant data. Alone, each Arabidopsis cell houses an estimated productivity, believes that Metanomics is on the right 15,000 to 30,000 chemicals. So perhaps it’s not sur- track. “They have a critical mass of well-trained scien- prising that Metanomics CEO Arno J. Krotzky says that tists, state-of-the-art instruments, and collaborations with important academic groups,” Dixon says. Al- During an average week, Metanomics though other bioinformatics companies exist, Meta- generates about 150 cloned and transformed nomics joins North Carolina–based Paradigm Genetics plant genes, 10,000 chromatographic in an elite group of businesses that do both extensive and mass-spectrometric measurements, plant metabolism experiments and software develop- and 150 gigabytes of data. ment. “In metabolic profiling, I think we are currently the reference stick other companies must measure up the company’s biggest hurdle has been organization. “It to,” Krotzky remarks. took us a while to adjust this really large technology Metanomics plans to branch into commercial crops platform,” says Krotzky, who compares the data jug- and plant products with the potential to produce drugs. gling with that done by Celera, which sequenced the hu- It may also begin testing the safety of genetically mod- man genome. “We’re working with thousands of living ified plants for biotech clients. After all, Krotzky notes, organisms. To control plant variability at a level that Metanomics already has the technology to compare shows minor changes in metabolic networks is a signif- conventional and modified plants at the metabolic lev- icant scientific challenge.” el. Along the way, he’d like the company’s scientists to Mindful of the stumbles of other biotech companies, uncover the functions behind all the estimated 27,000 Krotzky adds, Metanomics has worked quietly for four genes in Arabidopsis. But even for Metanomics, he con- years, completing internal proof-of-concept tests before cedes, that is a milestone that won’t be reached today making any public scientific claims. He says that the firm or tomorrow.

Razing the Tollbooths A call for restricting patents on basic biomedical research By GARY STIX

The Bayh-Dole Act, a 1980 law intended to prod the proliferation to inflammation in various maladies. Those commercialization of government-supported research, institutions and Ariad Pharmaceuticals (also in Cam- gave universities a major role in ushering in the new era bridge), the exclusive licensee of the patent, are now su- of biotechnology. The law fulfilled legislators’ most ing Eli Lilly, claiming that two of its drugs—one for os- ambitious expectations by encouraging the patenting teoporosis, one for sepsis—infringe the patent. Ariad of academic research—and the exclusive licensing of has contacted more than 50 other companies that are those patents to industry. In 1979 universities received researching or commercializing drugs that work a mere 264 patents—a number through this pathway, asking them for licensing fees that in 2000 rose to 3,764, and royalties. The broad-based patent does not protect about half of which went to specific drugs. Instead it has become a tollbooth for biomedical discoveries. The commercial drug research and development on the NF- 14-fold increase far outpaced κB pathway. “In this case, as in many others, upstream the overall growth in patents [precommercial] patents issued to academic institutions during that period. A few voic- serve as a tax on innovation, diluting rather than for- es in the intellectual-property tifying incentives for product development,” the au- community have now charged thors wrote in the winter-spring issue of Law and Con- that Bayh-Dole has gone too temporary Problems. (Their other article on the Bayh- far. Patents, they claim, have Dole Act appeared in the January-February issue of been granted on the fruits of American Scientist.) biomedical research that should Rai and Eisenberg suggest that the law should be al- remain in the public domain. tered to make it easier for the government—in particular, In recent co-authored articles, the National Institutes of Health—to specify that such Arti K. Rai of the University of upstream research remain public and not be subject to Pennsylvania and Rebecca S. Eisenberg of the Universi- patents. They also recommend facilitating the govern- ty of Michigan at Ann Arbor have proposed reform of ment’s ability to mandate the nonexclusive licensing of the law, contending that development of new biophar- a patent at reasonable rates. Both actions are permit- maceuticals and related technologies has been hindered ted under the current law but have almost never been by extending patent coverage beyond actual products exercised; the law makes it cumbersome to do so. to basic research findings. DNA sequences, protein Fiddling with Bayh-Dole does bear risks. For in- structures and disease pathways should, in many cas- stance, an executive-branch agency such as the NIH es, serve as a general knowledge base that can be used could be subject to political pressure in barring patents: freely by everyone. an administration opposed to using embryos in scien- Rai and Eisenberg cite the case of a patent obtained tific investigations might order an agency to withhold by teams at Harvard University, the Massachusetts In- patents on such research. But university technology- stitute of Technology and the Whitehead Institute for transfer offices, Rai and Eisenberg contend, cannot be Biomedical Research in Cambridge, Mass. It covers entrusted to make decisions about when to forgo patent- methods of treating disease by regulating cell-signaling ing, given that a big part of their mission is to bring in activity involving nuclear factor kappa B (NF-κB), licensing revenues. So more leverage is needed to ensure

JENNIFER KANE which controls genes for processes ranging from cell that basic biomedical research remains open to all.

I, Clone The Three Laws of Cloning will protect clones and advance science By MICHAEL SHERMER

In his 1950 science-fiction novel I, Robot, Isaac Asimov pre- among us is accounted for by genetics and the rest by environ- sented the Three Laws of Robotics: “1. A robot may not injure ment. It is impossible to duplicate the near-infinite number of a human being, or, through inaction, allow a human being to permutations that come into play during the development of come to harm. 2. A robot must obey the orders given it by hu- each individual, so cloning is no threat to unique personhood. man beings except where such orders would conflict with the The Playing God Myth has numerous promoters, among the First Law. 3. A robot must protect its own existence as long as latest being Stanley M. Hauerwas, a professor of theological such protection does not conflict with the First or Second Law.” ethics at Duke University: “The very attempt to clone a human The irrational fears people express today about cloning par- being is evil. The assumption that we must do what we can do allel those surrounding robotics half a century ago. So I would is fueled by the Promethean desire to be our own creators.” In like to propose Three Laws of Cloning that also clarify three mis- support of this myth, he is not alone. A 1997 Time/CNN poll understandings: 1. A human clone is a human revealed that 74 percent of 1,005 Americans being no less unique in his or her personhood Clone all you like— answered “yes” to the question “Is it against than an identical twin. 2. A human clone has all you’ll never God’s will to clone human beings?” Balder- the rights and privileges that accompany this le- produce another you. dash. Cloning may seem to be “playing God” gal and moral status. 3. A human clone is to be only because it is unfamiliar. Consider earli- accorded the dignity and respect due any member of our species. er examples of once “God-like” fertility technologies that are Although such simplifications risk erasing the rich nuances now cheerfully embraced because we have become accustomed found in ethical debates over pioneering research, they do aid to them, such as in vitro fertilization and embryo transfer. in attenuating risible fears often associated with such advances. The Human Rights and Dignity Myth is embodied in the It appears that the Raelians have not succeeded in Xeroxing Roman Catholic Church’s official statement against cloning, themselves, but it is clear that someone, somewhere, sometime based on the belief that it denies “the dignity of human procre- soon is going to generate a human clone. And once one team ation and of the conjugal union,” as well as in a Sunni Muslim has succeeded, it will be Katy bar the door for others to bring cleric’s demand that “science must be regulated by firm laws to on the clones. preserve humanity and its dignity.” Bunkum. Clones will be no If cloning produces genetic monstrosities that render it im- more alike than twins raised in separate environments, and no practical as another form of fertility enhancement, then it will one is suggesting that twins do not have rights or dignity or that not be necessary to ban it, because no one will use it. If cloning they should be banned. does work, however, there is no reason to forbid it, because the Instead of restricting or preventing the technology, I propose three common reasons given for implementing restrictions are that we adopt the Three Laws of Cloning, the principles of myths. I call them the Identical Personhood Myth, the Playing which are already incorporated in the laws and language of the God Myth, and the Human Rights and Dignity Myth. U.S. Constitution, and allow science to run its course. The soul The Identical Personhood Myth is well represented by ac- of science is found in courageous thought and creative experi- tivist Jeremy Rifkin: “It’s a horrendous crime to make a Xerox ment, not in restrictive fear and prohibitions. For science to proof someone. You’re putting a human into a genetic straitjack- gress, it must be given the opportunity to succeed or fail. Let’s et.” Baloney. He and fellow cloning critics have the argument run the cloning experiment and see what happens. bass ackward. As environmental determinists, they should be arguing: “Clone all you like—you’ll never produce another you, Michael Shermer is publisher of Skeptic magazine because environment matters as much as heredity.” The best sci- (www.skeptic.com) and general editor of The Skeptic

entiﬁc evidence to date indicates that roughly half the variance Encyclopedia of Pseudoscience. BRAD HINES

The Sudbury Neutrino Observatory has solved a 30-year-old mystery by showing that neutrinos from the sun change species en route to the earth

By Arthur B. McDonald, Joshua R. Klein and David L.Wark

Building a detector the size of a 10-story building two kilometers underground is a strange way to study solar phenomena. Yet that has turned out to be the key to unlocking a decades-old puzzle about the physical processes occurring inside the sun. Eng- lish physicist Arthur Eddington suggested as early as 1920 that nuclear fusion powered the sun, but efforts to confirm critical details of this idea in the 1960s ran into a stumbling block: experiments designed to detect a distinctive by-product of solar nuclear fusion reactions—ghostly particles called neutrinos—observed only a fraction of the expected number of them. It was not until last year, with the results from the underground Sudbury Neutrino Observatory (SNO) in

COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. Ontario, that physicists resolved this conundrum and thereby ing Davis’s all found similar results despite using a variety of fully confirmed Eddington’s proposal. different techniques. The number of neutrinos arriving from the Like all underground experiments designed to study the sun was always significantly less than the predicted total, in sun, SNO’s primary goal is to detect neutrinos, which are pro- some cases as low as one third, in others as high as three fifths, duced in great numbers in the solar core. But unlike most of the depending on the energies of the neutrinos studied. With no un- other experiments built over the previous three decades, SNO derstanding of why the predictions and the measurements were detects solar neutrinos using heavy water, in which a neutron so different, physicists had to put on hold the original goal of has been added to each of the water molecules’ hydrogen atoms studying the solar core by observing neutrinos. (making deuterium). The additional neutrons allow SNO to ob- While experimenters continued to run their neutrino exper- serve solar neutrinos in a way never done before, by counting iments, theorists improved the models used to predict the rate all three types, or “flavors,” of neutrino equally. Using this abil- of solar neutrino production. Those theoretical models are com- ity, SNO has demonstrated that the deficit of solar neutrinos plex, but they make only a few assumptions—that the sun is seen by earlier experiments resulted not from poor measure- powered by nuclear reactions that change the element abun- ments or a misunderstanding of the sun but from a newly dis- dances, that this power creates an outward pressure that is bal- covered property of the neutrinos themselves. anced by the inward pull of gravity, and that energy is trans- Ironically, the confirmation of our best theory of the sun ex- ported by photons and convection. The solar models continued poses the first flaw in the Standard Model of particle physics— to predict neutrino fluxes that exceeded the measurements, but our best theory of how the most fundamental constituents of other projections they made, such as the spectrum of helioseis- matter behave. We now understand the workings of the sun mologic vibrations seen on the solar surface, agreed very well better than we do the workings of the microscopic universe. with observations. The mysterious difference between the predictions and the The Problem measurements became known as the solar neutrino problem. THE FIRST SOLAR NEUTRINO EXPERIMENT, conduct- Although many physicists still believed that inherent difficul- ed in the mid-1960s by Raymond Davis, Jr., of the University ties in detecting neutrinos and calculating their production rate of Pennsylvania and his co-workers, was intended to be a tri- in the sun were somehow the cause of the discrepancy, a third umphant confirmation of the fusion theory of solar power gen- alternative became widely favored despite its somewhat revo- eration and the start of a new field in which neutrinos could lutionary implications. The Standard Model of particle physics be used to learn more about the sun. Davis’s experiment, lo- holds that there are three completely distinct, massless flavors cated in the Homestake gold mine near Lead, S.D., detected of neutrinos: the electron-neutrino, muon-neutrino and tau- neutrinos by a radiochemical technique. The detector contained neutrino. The fusion reactions in the center of the sun can pro- 615 metric tons of liquid tetrachloroethylene, or dry-cleaning duce only electron-neutrinos, and experiments like Davis’s were fluid, and neutrinos transformed atoms of chlorine in this flu- designed to look exclusively for this one flavor—at solar neu- id into atoms of argon. But rather than seeing one atom of ar- trino energies, only electron-neutrinos can convert chlorine gon created each day, as theory predicted, Davis observed just atoms to argon. But if the Standard Model were incomplete, one every 2.5 days. (In 2002 Davis shared the Nobel Prize with and the neutrino flavors were not distinct but instead mixed in Masatoshi Koshiba of the University of Tokyo for pioneering some way, then an electron-neutrino from the sun might trans- work in neutrino physics.) Thirty years of experiments follow- form into one of the other flavors and thus escape detection. The most favored mechanism for a change in neutrino flavor is neutrino oscillation [see illustration on page 44], which Overview/Oscillating Neutrinos requires that the neutrino flavors (electron-, muon- and tau-neu- ■ Since the 1960s, underground experiments have been trinos) are made up of mixtures of neutrino states (denoted as detecting far fewer electron-neutrinos from the sun than 1, 2 and 3) that have different masses. An electron-neutrino theory predicts. The mystery came to be known as the could then be a mixture of states 1 and 2, and a muon-neutrino solar neutrino problem. could be a different mixture of the same two states. Theory pre- ■ In 2002 the Sudbury Neutrino Observatory (SNO) resolved dicts that as they travel from the sun to the earth, such mixed the solar neutrino problem by determining that many of neutrinos will oscillate between one flavor and another. the electron-neutrinos produced inside the sun change to Particularly strong evidence of neutrino oscillation was pro- other flavors of neutrinos before reaching the earth, vided by the Super-Kamiokande collaboration in 1998, which ) causing them to go undetected by past experiments. found that muon-neutrinos produced in the upper atmosphere ■ SNO’s result confirms that we understand how the sun is by cosmic rays were disappearing with a probability that de- powered and implies that neutrinos, long thought to be pended on the distance they traveled. This disappearance is ex-

massless, have masses. The Standard Model of particle plained extremely well by neutrino oscillations, in this case preceding pages physics, which is otherwise extraordinarily successful, muon-neutrinos that are probably turning into tau-neutrinos. must be modified to accommodate this change. The former are easily detected by Super-Kamiokande at cos-

mic-ray energies, but the latter mostly evade detection [see “De- SLIM FILMS (

42 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. tecting Massive Neutrinos,” by Edward Kearns, Takaaki Kaji- first two seconds of travel through the sun itself, an effect caused ta and Yoji Totsuka; Scientific American, August 1999]. by the different ways in which each neutrino flavor interacts A similar process could explain the solar neutrino deficit. In with matter. Each scenario requires its own specific range of neu- one scenario, the neutrinos would oscillate during their eight- trino parameters—mass differences and the amount of intrinsic minute journey through the vacuum of space from the sun to the mixing of the flavors. Despite the evidence from Super-Kami- earth. In another model, the oscillation is enhanced during the okande and other experiments, however, it remained possible ) next two pages ); SLIM FILMS ( photograph

PHOTOMULTIPLIER TUBES—more than 9,500 of them—on a geodesic sphere of light. The entire assembly is suspended in ordinary water. All the 18 meters in diameter act as the eyes of the Sudbury Neutrino Observatory. materials that make up the detector must be extraordinarily free of natural The tubes surround and monitor a 12-meter-diameter acrylic sphere that traces of radioactive elements to avoid overwhelming the tubes with

COURTESY OF SUDBURY NEUTRINO OBSERVATORY ( contains 1,000 tons of heavy water. Each tube can detect a single photon false solar neutrino counts.

HOW NEUTRINOS OSCILLATE An electron-neutrino (left) is actually a superposition of a type 1 and a type 2 neutrino with their quantum waves in phase. Because the type 1 and type 2 waves have different wavelengths, after traveling a distance they go out of phase, making a muon- or a tau-neutrino (middle). With further travel the neutrino oscillates back to being an electron-neutrino (right).

TYPE 1 NEUTRINO

ELECTRON- NEUTRINO ELECTRON- NEUTRINO

TYPE 2 NEUTRINO MUON- OR TAU-NEUTRINO

ELECTRON- ELECTRON- MUON- OR DAYTIME NIGHTTIME NEUTRINOS NEUTRINOS TAU-NEUTRINOS RESULTS CREATED RESULTS

OSCILLATION IN SUN OSCILLATION IN VACUUM OSCILLATION IN EARTH

WHERE NEUTRINOS OSCILLATE The electron-neutrinos produced at the center of the sun may oscillate while they are still inside the sun or after they emerge on their eight-minute journey to the earth. Which oscillation occurs depends on details such as the mass differences and the intrinsic degree of mixing of type 1 and 2 neutrinos. Extra oscillation may also occur inside the earth, which manifests as a difference between daytime and nighttime results.

ACTUAL DATA OF A CANDIDATE NEUTRINO EVENT HOW SNO DETECTS NEUTRINOS The Sudbury Neutrino Observatory, or SNO (opposite page), detects a neutrino by seeing a characteristic ring of Cerenkov light emitted by a high-speed electron. The neutrino produces the energetic electron in SNO's heavy water (large blue sphere) in one of three ways. In deuteron breakup (a), the neutrino (blue) splits a deuterium nucleus into its component proton (purple) and neutron (green). The neutron eventually combines with another deuteron, releasing a gamma ray (wavy line), which in turn knocks free an electron (pink) whose Cerenkov light (yellow) is detected. In neutrino absorption (b) a neutron absorbs the neutrino and is thereby turned into a proton and an energetic electron. Only electron- neutrinos can be absorbed in this way. Less often the neutrino may collide directly with an electron (c). Cosmic- ray muons (red) are distinguished from neutrinos by the amount of Cerenkov light they produce and where they produce it—outside the detector as well as inside. The number of muons is reduced to manageable levels by positioning the detector two kilometers underground.

COSMIC-RAY MUON NEUTRON

GAMMA RAY

ELECTRON CERENKOV LIGHT PROTON

c b ELECTRON- ANY NEUTRINO NEUTRINO

ENERGETIC ELECTRON

PROTON

EMPIRE STATE BUILDING

SNO (6,800 FEET DEEP) COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. that neutrinos were disappearing by some process other than neutrino absorption and deuteron breakup for solar neutrinos. oscillation. Until 2001 scientists had no direct evidence of so- Chen’s proposal led to the establishment of the SNO sci- lar neutrino oscillation, in which the transformed solar neutri- entific collaboration and ultimately to the creation of the SNO nos themselves were detected. detector. The 1,000 tons of heavy water are held in a 12-meter- diameter transparent acrylic vessel. The heavy water is viewed The Observatory by more than 9,500 photomultiplier tubes held on an 18-me- THE SUDBURY NEUTRINO OBSERVATORY was designed ter-diameter geodesic sphere [see illustration on page 43]. Each to search for this direct evidence, by detecting neutrinos using tube is capable of detecting a single photon of light. The entire several different interactions with its 1,000 tons of heavy wa- structure is submerged in ultrapure ordinary water filling a cav- ter. One of these reactions exclusively counts electron-neutri- ity carved out of the rock two kilometers below the surface of nos; the others count all flavors without distinguishing among the earth. them. If the solar neutrinos arriving at the earth consisted only of electron-neutrinos—and therefore no flavor transformation SNO’s Measurement was occurring—then the count of neutrinos of all flavors would SOLAR NEUTRINOS CAN BE OBSERVED deep underground be the same as the count of electron-neutrinos alone. On the because of the extreme weakness of their interaction with mat- other hand, if the count of all flavors was far in excess of the ter. During the day, neutrinos easily travel down to SNO count of the electron-neutrinos, that would prove that neutri- through two kilometers of rock, and at night they are almost nos from the sun were changing flavor. equally unaffected by the thousands of kilometers that they trav- The key to SNO’s ability to count both electron-neutrinos el up through the earth. Such feeble coupling makes them in- alone and all flavors is the heavy water’s deuterium nuclei, also teresting from the perspective of solar astrophysics. Most of the called deuterons. The neutron in a deuteron produces two sep- energy created in the center of the sun takes millions of years to arate neutrino reactions: neutrino absorption, in which an elec- reach the solar surface and leave as sunlight. Neutrinos, in con- tron-neutrino is absorbed by a neutron and an electron is cre- trast, emerge after two seconds, coming to us directly from the ated, and deuteron breakup, in which a deuterium nucleus is point where solar power is created. broken apart and the neutron liberated. Only electron-neutri- With neither the whole sun nor the entire earth able to im- nos can undergo neutrino absorption, but neutrinos of any fla- pede the passage of neutrinos, capturing them with a detector vor can break up deuterons. A third reaction detected by SNO, weighing just 1,000 tons poses something of a challenge. But the scattering of electrons by neutrinos, can also be used to although the vast majority of neutrinos that enter SNO pass count neutrinos other than electron-neutrinos but is much less through it, on very rare occasions, one will—by chance alone— sensitive to muon- and tau-neutrinos than the deuteron collide with an electron or an atomic nucleus and deposit breakup reaction [see illustration on preceding page]. enough energy to be observed. With enough neutrinos, even the SNO was not the first experiment to use heavy water. In the rarity of these interactions can be overcome. Luckily, the sun’s 1960s T. J. Jenkins and F. W. Dix of Case Western Reserve Uni- neutrino output is enormous—five million high-energy solar versity used heavy water in a very early attempt to observe neu- neutrinos pass through every square centimeter of the earth trinos from the sun. They used about 2,000 liters (two tons) of every second—which leads to about 10 neutrino events, or in- heavy water aboveground, but the signs of solar neutrinos were teractions, in SNO’s 1,000 tons of heavy water every day. The swamped by the effects of cosmic rays. In 1984 Herb Chen of three types of neutrino reaction that occur in SNO all generate the University of California at Irvine proposed bringing 1,000 tons energetic electrons, which are detectable through their proof heavy water from Canada’s CANDU nuclear reactor to the bot- duction of Cerenkov light—a cone of light emitted like a shock tom of INCO Ltd.’s Creighton nickel mine in Sudbury—a loca- wave by the fast-moving particle. tion that was deep enough to enable a clear measurement of both This small number of neutrino events, however, has to be

EIGHT DECADES OF THE SUN AND NEUTRINOS

IT HAS TAKEN MOST OF A CENTURY 1920 1940 to verify fully that we understand how the sun generates its power. Along the way, neutrinos have 1920 Arthur Eddington 1930 Wolfgang Pauli rescues 1938 Hans Bethe 1956 Frederick Reines gone from speculative hypothesis proposes that the sun conservation of energy by analyzes the basic nuclear and Clyde Cowan first to key experimental tool. Their is powered by nuclear hypothesizing an unseen processes that could detect the neutrino oscillations point to fundamental fusion converting particle, the neutrino, that power the sun and using the Savannah new physics to be discovered in hydrogen atoms carries away energy from accurately estimates the River nuclear reactor the decades to come. into helium some radioactive decays sun's central temperature

46 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. Five million high-energy distinguished from flashes of Cerenkov light caused by other particles. In particular, cosmic-ray muons are created continu- solar neutrinos ally in the upper atmosphere, and when they enter the detector they can produce enough Cerenkov light to illuminate every pass through every square photomultiplier tube. The intervening kilometers of rock between the earth’s surface and SNO reduce the deluge of cosmic- centimeter of your body ray muons to a mere trickle of just three an hour. And although every second. three muons an hour is a far greater rate than the 10 neutrino interactions a day, these muons are easy to distinguish from neutrino events by the Cerenkov light they produce in the or- amine many events. For example, deuteron breakup, the split- dinary water outside the detector. ting of a deuterium nucleus in the heavy water, always leads A far more sinister source of false neutrino counts is the in- to a gamma ray of the same energy, whereas the electrons pro- trinsic radioactivity in the detector materials themselves. Every- duced by neutrino absorption and electron scattering have a thing inside the detector—from the heavy water itself to the broad spectrum of energies. Similarly, electron scattering pro- acrylic vessel that holds it to the glass and steel of the photo- duces electrons that travel away from the sun, whereas the multiplier tubes and support structure—has trace amounts of Cerenkov light from deuteron breakup can point in any direc- naturally occurring radioactive elements. Similarly, the air in tion. Finally, the locations where the reactions occur differ as the mine contains radioactive radon gas. Every time a nucleus well—electron scattering, for instance, occurs as easily in the in these radioactive elements decays inside the SNO detector, outer layer of light water as in the heavy water; the other reac- it can release an energetic electron or gamma ray and ultimately tions do not. With an understanding of those details, SNO re- produce Cerenkov light that mimics the signal of a neutrino. searchers can statistically determine how many of the observed The water and the other materials used in SNO are purified to events to assign to each reaction. remove the bulk of the radioactive contaminants (or were cho- Such an understanding is the result of measurements that sen to be naturally pure), but even parts per billion are enough were complete nuclear physics experiments in their own right: to overwhelm the true neutrino signal with false counts. to determine how to measure energy using Cerenkov light, The task before SNO is therefore very complex—it must sources of radioactivity with known energies were inserted in- count neutrino events, determine how many are caused by each side the detector. To measure how the Cerenkov light travels of the three reactions, and estimate how many of the apparent through and reflects off the various media in the detector (the neutrinos are caused by something else, such as radioactive con- water, the acrylic, the photomultiplier tubes), a variable wave- tamination. Errors as small as a few percent in any of the steps length laser light source was used. The effects of radioactive of analysis would render meaningless SNO’s comparison of the contamination were assessed by similar experiments, including electron-neutrino flux to the total neutrino flux. Over the 306 radioassays of the water using new techniques designed specif- days of running, from November 1999 to May 2001, SNO ically for SNO. recorded nearly half a billion events. By the time the data re- For the final SNO data set, after statistical analysis, 576 duction was complete, only 2,928 of these remained as candi- events were assigned to deuteron breakup, 1,967 events to neu- date neutrino events. trino absorption and 263 to electron scattering. Radioactivity SNO cannot uniquely determine whether a given candidate and other backgrounds caused the remaining 122. From these neutrino event was the result of a particular reaction. Typical- numbers of events, we must calculate how many actual neu- ly an event like the one shown on page 44 could equally well be trinos must be passing through SNO, based on the tiny proba- the result of deuteron breakup as neutrino absorption. Fortu- bilities that any particular neutrino will break up a deuteron,

nately, differences between the reactions show up when we ex- be absorbed or scatter an electron. The upshot of all the calcu- BRYAN CHRISTIE DESIGN

1960 1980 2000

1964 1967 Raymond Davis, 1969 Vladimir Gribov 1978 and 1985 1998 2002 SNO confirms 2002 KamLAND John Bahcall Jr., first measures and Bruno Pontecorvo Stanislav Mikheyev, Super-Kamiokande that electron- experiment predicts the neutrinos from the propose that neutrino Alexei Smirnov and assembles neutrinos from the detects neutrino flux sun, using 600 tons oscillations explain the Lincoln Wolfenstein evidence of sun are oscillating to oscillation of expected to be of dry-cleaning fluid anomalously small posit that matter can neutrino oscillation another flavor, fully antineutrinos observed from in a mine in Lead, S.D. number of neutrinos enhance neutrino in cosmic-ray resolving the solar emitted from the sun detected oscillations neutrinos neutrino problem nuclear reactors

www.sciam.com SCIENTIFIC AMERICAN 47 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. Some Other Neutrino Experiments HOMESTAKE: Solar neutrino detector located in the Homestake GRAN SASSO: The world’s largest underground laboratory, gold mine in Lead, S.D. The original chlorine experiment, accessed via a highway tunnel, located under the Gran Sasso started in 1966, used 600 tons of dry-cleaning fluid. Mountains about 150 kilometers east of Rome. Solar neutrino Supplemented in 1996 by a radiochemical sodium iodide experiments include Gallex/GNO, which began in 1991 and experiment using 100 tons of iodine. uses 30 tons of gallium (as aqueous gallium trichloride), and Borexino, a sphere of 300 tons of scintillator viewed by 2,200 KAMIOKA: Houses Super-Kamiokande, a 50,000-ton light- photomultipliers, scheduled for completion this year. water detector studying cosmic-ray and solar neutrinos, as well as muon-neutrinos beamed from the KEK facility MINIBOONE (Booster Neutrino Experiment): Located at 250 kilometers away (“K2K” experiment). Also houses Fermilab in Illinois. Beams of muon-neutrinos and anti-muon- KamLAND, a smaller detector (1,000 tons of liquid scintillator, neutrinos travel through 500 meters of earth to be detected in which emits light when a charged particle passes through) an 800-ton tank of mineral oil. Endeavoring to test a contro- that counts anti-electron-neutrinos emitted by all the nuclear versial result reported by the LSND experiment at Los Alamos reactors nearby in South Korea and Japan. National Lab in 1995. Began collecting data in September 2002.

SAGE (Russian-American Gallium Solar Neutrino Experiment): MINOS: Will beam neutrinos from Fermilab to the Soudan Located at Baksan in the Caucasus Mountains in Russia. Uses detector, 735 kilometers away in Minnesota. Detector is 5,400 50 tons of gallium, which is capable of detecting the low- tons of iron laced with plastic particle detectors. Projected to energy neutrinos produced by proton-proton fusion in the sun. begin taking data in 2005.

lations is that the observed 1,967 neutrino absorption events completely explain the deficit observed for the past 30 years? It represent 1.75 million electron-neutrinos passing through each does: the deduced 5.09 million neutrinos agrees remarkably square centimeter of the SNO detector every second. That is well with the predictions of solar models. We can now claim only 35 percent of the neutrino flux predicted by solar models. that we really do understand the way the sun generates its pow- SNO thus first confirms what other solar neutrino experiments er. Having taken a detour lasting three decades, in which we have seen—that the number of electron-neutrinos arriving from found that the sun could tell us something new about neutri- the sun is far smaller than solar models predict. nos, we can finally return to Davis’s original goal and begin to The critical question, however, is whether the number of use neutrinos to understand the sun. For example, neutrino electron-neutrinos arriving from the sun is significantly small- studies could determine how much of the sun’s energy is pro- er than the number of neutrinos of all flavors. Indeed, the 576 duced by direct nuclear fusion of hydrogen atoms and how events assigned to deuteron breakup represent a total neutri- much is catalyzed by carbon atoms. no flux of 5.09 million per square centimeter per second—far larger than the 1.75 million electron-neutrinos measured by The Future neutrino absorption. These numbers are determined with high THE IMPLICATIONS OF SNO’SDISCOVERY go even fur- accuracy. The difference between them is more than five times ther. If neutrinos change flavor through oscillation, then they the experimental uncertainty. cannot be massless. After photons, neutrinos are the second The excess of neutrinos measured by deuteron breakup most numerous known particles in the universe, so even a tiny means that nearly two thirds of the total 5.09 million neutrinos mass could have a significant cosmological significance. Neu- arriving from the sun are either muon- or tau-neutrinos. The trino oscillation experiments such as SNO and Super-Kami- sun’s fusion reactions can produce only electron-neutrinos, so some of them must be transformed on their way to the earth. ARTHUR B. MCDONALD, JOSHUA R. KLEIN and DAVID L. WARK are SNO has therefore demonstrated directly that neutrinos do not members of the 130-strong Sudbury Neutrino Observatory (SNO) behave according to the simple scheme of three distinct mass- collaboration. McDonald, a native of Sydney, Nova Scotia, has been less flavors described by the Standard Model. In 20 years of try- the director of the SNO Institute since its inception in 1989. He is ing, only experiments such as Super-Kamiokande and SNO also professor of physics at Queen’s University in Kingston, On- have shown that the fundamental particles have properties not tario. Klein received his Ph.D. from Princeton University in 1994 and contained in the Standard Model. The observations of neutri- THE AUTHORS began his work on SNO at the University of Pennsylvania. He is now no flavor transformation provide direct experimental evidence assistant professor of physics at the University of Texas at Austin. that there is yet more to be discovered about the microscopic Wark has spent the past 13 years in the U.K., at the University of universe. Oxford, the University of Sussex and the Rutherford Appleton Lab- But what of the solar neutrino problem itself—does the dis- oratory, trying to explain the infield fly rule to cricket fans. He has covery that electron-neutrinos transform into another flavor worked on a number of neutrino experiments in addition to SNO.

48 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. Future neutrino experiments okande measure only mass differences, not masses themselves. Showing that mass differences are not zero, however, proves might help explain why that at least some of the masses are not zero. Combining the oscillation results for mass differences with upper limits for the the universe is made of electron-neutrino mass from other experiments shows that neutrinos make up something between 0.3 and 21 percent of the matter rather than antimatter. critical density for a flat universe. (Other cosmological data strongly indicate that the universe is flat.) This amount is not The KamLAND results imply neutrino mass differences and negligible (it is roughly comparable to the 4 percent density that mixing parameters similar to those seen by SNO. arises from gas, dust and stars), but it is not quite enough to ex- Future neutrino experiments might probe one of the biggest plain all the matter that seems to be present in the universe. Be- mysteries in the cosmos: Why is the universe made of matter cause neutrinos were the last known particles that could have rather than antimatter? Russian physicist Andrei Sakharov first made up the missing dark matter, some particle or particles not pointed out that to get from a big bang of pure energy to the currently known to physics must exist—and with a density far current matter-dominated universe requires the laws of phys- in excess of everything we do know. ics to be different for particles and antiparticles. This is called SNO has also been searching for direct evidence of the ef- CP (charge-parity) violation, and sensitive measurements of fects of matter on neutrino oscillations. As mentioned earlier, particle decays have verified that the laws of physics violate CP. travel through the sun can enhance the probability of oscilla- The problem is that the CP violation seen so far is not enough tions. If this occurs, the passage of neutrinos through thousands to explain the amount of matter around us, so phenomena we of kilometers of the earth could lead to a small reversal in the have not yet observed must be hiding more CP violation. One process—the sun might shine more brightly in electron-neutri- possible hiding place is neutrino oscillations. nos at night than during the day. SNO’s data show a small ex- To observe CP-violating neutrino oscillations will be a multi- cess of electron-neutrinos arriving at night compared with dur- stage process. First physicists must see electron-neutrinos ap- ing the day, but as of now the measurement is not significant pear in intense beams of muon-neutrinos. Second, higher-in- enough to decide whether the effect is real. tensity accelerators must be built to produce beams of neutri- The results reported by SNO so far are just the beginning. nos so intense and pure that their oscillations can be observed For the observations cited here, we detected the neutrons from in detectors located across continents or on the other side of the the critical deuteron breakup events by observing their capture earth. Studies of a rare radioactive process called neutrinoless by other deuterium atoms—an inefficient process that produces double beta decay will provide further information about neu- little light. In May 2001 two tons of highly purified sodium trino masses and CP violation. chloride (table salt) were added to the heavy water. Chlorine It will probably be more than a decade before these exper- nuclei capture neutrons with much higher efficiency than deu- iments become a reality. A decade may seem a long way off, but terium nuclei do, producing events that have more light and are the past 30 years, and the sagas of experiments such as SNO, easier to distinguish from background. Thus, SNO will make have shown that neutrino physicists are patient and very per- a separate and more sensitive measurement of the deuteron sistent—one has to be to pry out the secrets of these elusive par- breakup rate to check the first results. The SNO collaboration ticles. These secrets are intimately tied up with our next level of has also built an array of ultraclean detectors called propor- understanding of particle physics, astrophysics and cosmolo- tional counters, which will be deployed throughout the heavy gy, and thus persist we must. water in mid-2003 to look for the neutrons directly. Making these detectors was a technical challenge of the first order be- A broadcast version cause they must have a spectacularly low level of intrinsic ra- of this article will air dioactive background—corresponding to about one count per March 25 on National meter of detector per year. Those devices will essentially check Geographic Today, a SNO’s earlier results by an independent experiment. program on the National SNO has unique capabilities, but it is not the only game in Geographic Channel. Please check your local listings. town. In December 2002 the first results from a new Japanese- American experiment called KamLAND were reported. The KamLAND detector is at the Super-Kamiokande site and stud- MORE TO EXPLORE ies electron-antineutrinos produced by all the nuclear reactors The Origin of Neutrino Mass. Hitoshi Murayama in Physics World, Vol. 15, nearby in Japan and Korea. If matter-enhanced neutrino oscil- No. 5, pages 35–39; May 2002. lations explain the flavor change seen by SNO, theory predicts The Asymmetry between Matter and Antimatter. Helen R. Quinn in that these antineutrinos should also change flavor over dis- Physics Today, Vol. 56, No. 2, pages 30–35; February 2003. tances of tens or hundreds of kilometers. Indeed, KamLAND The SNO Web site is at www.sno.phy.queensu.ca has seen too few electron-antineutrinos, implying that they are The Neutrino Oscillation Industry Web site, maintained by Argonne oscillating en route from the nuclear reactors to the detector. National Laboratory, is at www.neutrinooscillation.org

How to get drugs where they they n eed to go Where a Pill Won’t Reach

www.sciam.com SCIENTIFIC AMERICAN 51 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. From the point of view of a drug, it’s a long trip from the pill bottle to an ache or the site of an infection. After someone swallows a medicine, the into the blood as easily as more typical wafer that can be implanted into the chemical must traverse a veritable maze. drugs, which generally consist of small brain to administer chemotherapy di- It has to survive a journey through the molecules. Coatings also have a limited rectly to brain tumors. Already available stomach and reach the intestines intact ability to control a drug’s pharmacoki- in Europe and coming soon in the U.S. before crossing the intestinal wall into netics—the rate at which it enters circu- will be polymer-coated, drug-releasing circulation. Once in the blood, it gets ﬁl- lation and the time it persists in the stents, which so far have shown remark- tered through the liver before it can trav- body’s tissues and organs. A drug can be able results in keeping blood vessels open el to the rest of the body. At each “way toxic if it gets into the bloodstream too after a clot-clearing procedure called station,” the compound must resist the quickly at high concentrations or if it angioplasty. acids of digestive juices, jump membrane sticks around too long; conversely, it can Indeed, scientists have been exploring barriers or fend off enzymes designed to be ineffective if a protracted delay occurs nearly every part of the body—the skin, chop it into useless bits. before it begins circulating. the nose, the lungs, as well as the intes- Pharmaceutical makers have come up Injecting a drug avoids the obstacles tine—as portals for introducing drug with various solutions to help certain posed by the stomach and the intestinal payloads. In the process, they have de- medicines on the market today surpass tract, but many patients are understand- vised noninvasive ways to deliver com- these obstacles; however, these approach- ably reluctant to give themselves shots re- plex molecules, such as using ultrasound es do not work for many other drugs. peatedly or to visit a doctor every day. to blast drugs through the skin painless- One strategy, for instance, coats pills Accordingly, scientists have sought a bet- ly. They have also combined advances in with a shell that is insoluble in stomach ter way. Over the past two decades a nanotechnology and microfabrication to secretions but that dissolves readily once spate of alternative drug delivery systems make implantable microchips that can it hits the more alkaline environment of have been designed: sales of drugs ad- deliver drugs precisely and on schedule. the small intestine. But if a drug is made ministered by patch, implant, long-acting of protein—as most agents produced us- injection, topical gel, controlled-release Breaching the Wall ing biotechnology are—it also has to pill, or nasal or lung spray now exceed A VARIETY OF GROUPS have been us- evade the activity of protein-destroying $20 billion a year in the U.S. alone. Two ing the new technologies to solve the enzymes called proteases. Packaging pills notable examples approved recently by problem of penetrating the intestinal wall. with their own bodyguards (in this case, the Food and Drug Administration are Edith Mathiowitz of Brown University molecules called protease inhibitors) Nutropin Depot—injectable, degradable and her colleagues, for example, have de- could enable protein-based drugs to sur- polymer microspheres that secrete hu- veloped a way to entrap proteins in ex- vive, but it would not aid them in cross- man growth hormone for up to four tremely tiny blobs of a gluey substance ing the gut lining; they are too big to slip weeks between shots—and Gliadel, a called a bioadhesive, which can penetrate through and between intestinal cells. The concept of using bioadhesion to enable Overview/Drug Delivery orally administered drugs to attach to mu- ■ Many drugs—especially the protein-based pharmaceuticals made using cous membranes had its origins in work biotechnology—are broken down quickly if taken orally. conducted in the 1970s and 1980s in the ■ Accordingly, researchers are developing new means of administering medicines, laboratories of Tsuneji Nagai of Hoshi including wearable devices that use pulses of electricity or ultrasound to drive University in Tokyo, Joseph R. Robinson drugs through the skin painlessly. of the University of Wisconsin–Madison ■ The future promises implantable microchips that deliver drugs in preprogrammed and Nicholas A. Peppas of Purdue Uni- doses and that communicate with computers in physicians’ offices. versity (he is now at the University of Texas at Austin). Until 10 years ago the

52 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. insulin that can be given orally. (Many GETTING PAST THE GUT new drug delivery approaches focus on HURDLES: Digestive acids and enzymes degrade drugs before they can reach insulin because it is a protein that must their targets; drugs have difficulty piercing the intestinal wall be injected regularly by people with type 1 diabetes.) In animal tests, the poly- SOLUTIONS: (a) Coat drugs with bioadhesive polymers that bind to the gut lining anhydride shows promise with both hy- and squeeze between cells; (b) link drugs to targeting molecules that home in on drophilic and hydrophobic proteins. receptors on intestinal cells that allow the drugs to be taken up; (c) attach Peppas and his co-workers have also drugs to carrier molecules that escort them into cells developed polymers that are not only bioadhesive but swell in response to a pH SOME COMPANIES WORKING ON THE PROBLEM: change. They are able to protect a protein Biotech Australia, Roseville, New South Wales drug such as insulin from the acidic pH of Emisphere Technologies, Tarrytown, N.Y. the stomach and then release it in the more alkaline pH of the intestine. The polymers are also able to protect the pro- acb Carrier Bioadhesive- molecule tein from proteases in the upper small in- coated drug Targeting molecule testine and can temporarily open the connections between intestinal cells, allowing Drug Receptor the protein to pass through. Another strategy to deliver protein- based drugs orally is to encase them in carrier molecules that can ferry them across the gut lining. Emisphere Technologies in Tarrytown, N.Y., has developed a series of molecular carriers that appear to squeeze proteins to make them smaller so Gut mucosa cell Nucleus they can cross cell membranes more readily. Once the carrier does its job of getting the drug inside a cell, it breaks away and allows the protein to spring back into its native—and therefore active—form. Emi- sphere is testing the strategy to administer insulin to diabetics and to deliver the Blood vessel blood-thinning protein heparin to people Scientists have been exploring nearly every part of the body—the skin, the nose, the lungs, as well as the intestine—as portals for introducing drug payloads.

most promising bioadhesive polymers drophobic (water-repelling) bioadhesive undergoing hip-replacement surgery, seemed to be water-loving plastics called polymers called polyanhydrides, which who sometimes experience blood clots. hydrophilic polymers and hydrogels. From expose carboxyl groups on their exteri- Other scientists have been working to these early studies, researchers inferred ors as their surfaces erode, can bind to couple drug proteins to molecules that that the most “wettable” polymers— the gut lining just as well as hydrophilic target speciﬁc receptors in the gastroin- those with the highest concentrations of polymers but can cross the intestinal mu- testinal tract. One of the early examples carboxyl groups—were the materials of cosa and enter the bloodstream more is the work of Gregory J. Russell-Jones of choice for bioadhesion. Although they readily. One polyanhydride in particu- Biotech Australia in Roseville, New would stick to the intestinal mucosa, how- lar—poly(fumaric-co-sebacic anhydride)— South Wales, who exploited the fact that ever, they did not penetrate it very well, showed greater adhesive forces than any cells in the intestine use receptors to grab and they released the protein too quickly. other material tested. The technology is vitamin B12 and transport it through the In 1997 Mathiowitz found that hy- now being explored to make a form of gut wall. He found that by linking a pro-

www.sciam.com SCIENTIFIC AMERICAN 53 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. tein to vitamin B12, he could trick the vitamin receptors into taking up the protein as well as the vitamin. But there are only PENETRATING THE SKIN so many vitamin B12 receptors in the gut, HURDLES: Tough stratum corneum (skin’s outer layer) blocks drug entry; and they might not be abundant enough large molecules have difficulty crossing the epidermis to the blood vessels to drag a given protein drug into the in the dermis blood in the amounts needed for a therapeutic effect. Other scientists are now SOLUTIONS: Iontophoresis (below) uses painless pulses of electricity to make looking to harness lectins—plentiful, skin permeable; ultrasound employs sound waves that temporarily make tiny sticky molecules that constitute part of the channels in the stratum corneum connective tissue between intestinal cells— or other substances to do the job. SOME COMPANIES WORKING ON THE PROBLEM: ALZA, Mountain View, Calif. Patching It Up Sontra Medical, Cambridge, Mass. THE INTESTINE is a fairly direct route Vyteris, Fair Lawn, N.J. to the bloodstream, but the skin is much more accessible. Although skin can be a relatively impermeable barrier, a few Cord to power supply drugs have just the right physical and chemical characteristics to cross it at reasonable rates. Transdermal patches that SKIN last up to seven days are now on the market: nicotine to help people stop smoking Positive electrode Negative electrode and estradiol (estrogen) to counter the symptoms of menopause or to act as part of a contraceptive [see “Potent Patches,” Working Knowledge, page 92]. Drug Passing a small, direct electric current Stratum corneum through the skin can make the epidermis permeable to many other drugs—including proteins. Scientists at ALZA in Moun- tain View, Calif., and at Vyteris, a spin- off of Becton Dickinson based in Fair Lawn, N.J., are independently conduct- Blood vessel ing advanced clinical trials using the technique, known as iontophoresis. In general, iontophoresis employs two patches— Ultrasound has also been harnessed to tragotri, a former graduate student in my one negatively charged and one positively enhance skin permeability. Joseph Kost— lab, and I have used ultrasound to in- charged—that are linked to a reservoir of a former postdoctoral fellow and visiting crease up to 5,000 times the ability of pro- a given drug. A painless pulse of electric- scientist in my laboratory and now a proteins the size of insulin to diffuse through ity can drive drugs, which tend to be fessor at Ben-Gurion University in Israel— the skin. Sontra Medical in Cambridge, charged, through the impermeable outer discovered that ultrasound can tem- Mass., which I co-founded and where layer of the epidermis and into the blood porarily disorder the skin’s outermost lay- Kost is chief scientiﬁc ofﬁcer, is testing the vessels of the dermis. Vyteris, for exam- er, the stratum corneum, the principal technique for administering insulin and ple, has applied for FDA approval to mar- barrier to drug diffusion. My M.I.T. col- pain medications. The ultrasound device ket its iontophoresis system to deliver the league Daniel Blankschtein, Samir Mi- uses a short (15-second) burst of energy painkiller lidocaine. The system’s battery source is small enough to wear under- ROBERT LANGER is Kenneth J. Germeshausen Professor of Chemical and Biomedical Engi- neath clothing. The company is planning neering at the Massachusetts Institute of Technology. He is also a director of a number of clinical tests of its device’s ability to ad- companies, including Sontra Medical and MicroCHIPS. In 2002 he received the Charles Stark minister daily doses of parathyroid hor- Draper Prize, which is considered the equivalent of the Nobel Prize for engineering. In 1998 mone to patients with osteoporosis or he was granted the Lemelson-M.I.T. Prize for being “one of history’s most prolific inventors pulses of gonadotropin-releasing hor- THE AUTHOR in medicine.” Langer is one of the few individuals to have ever been elected to all three of mone every 90 minutes to women prepar- the U.S. national academies: the Institute of Medicine, the National Academy of Sciences, ing for in vitro fertilization procedures. and the National Academy of Engineering.

54 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. much weaker than that employed for di- Inhaling the Future as protein-based drugs. It has been difﬁ- agnostic imaging to make the skin more LUNG DELIVERY represents another cult, however, to design inhaler devices permeable in a particular spot for up to important opportunity and challenge— that can produce a sufﬁcient number of 24 hours. The ultrasonic horn of the whether for treating lung conditions or aerosol particles small enough to pene- handheld device vibrates at 55,000 cycles for administering a drug to the blood- trate deeply into the lung, without wast- a second (55 kilohertz) in a liquid medi- stream quickly to treat diseases elsewhere ing the drug. (Most conventional inhalers, um coupled to the skin. The low-fre- in the body. The lungs consist of micro- such as those used to treat asthma, deliv- quency ultrasonic energy creates tiny bub- scopic sacs called alveoli that are linked er less than 10 percent of their contents.) bles that expand and contract in the cou- directly to blood vessels. During breath- Immune cells in the lung called macro- pling medium and in the cell membranes ing, oxygen enters the blood through the phages can also clear most drugs rapidly. of the stratum corneum, in effect drilling alveoli, and the waste product carbon A variety of researchers and compa- temporary miniature channels through dioxide exits. A similar process can also nies are now working on improved in- which drugs can enter. admit aerosols of larger molecules, such haler designs that administer extremely A painless pulse of electricity can drive drugs, which tend to be charged, through the outer layer of the epidermis and into the blood vessels of the dermis.

ﬁne mists in an efﬁcient manner. One such inhaler, developed by Aradigm in ENTERING THE LUNGS Hayward, Calif., for liquid formulations, HURDLES: Penetrating the air sacs, or alveoli; avoiding destruction by immune pushes a given drug through small noz- cells called macrophages zles that can be preprogrammed to deliver particular doses. Another approach, SOLUTIONS: Optimize the size of aerosol particles (liquid or powder) so they developed by Nektar Therapeutics (pre- can reach deep into the lungs; prevent the aerosol particles from sticking viously called Inhale Therapeutic Sys- together so they can form a fine mist tems) in San Carlos, Calif., can generate an aerosol cloud from a dry powder by SOME COMPANIES WORKING ON THE PROBLEM: compressing air into it and breaking it Alkermes, Cambridge, Mass. into tiny particles capable of reaching the Aradigm, Hayward, Calif. deepest areas of the lung. Both compa- Nektar Therapeutics (formerly Inhale Therapeutic Systems), San Carlos, Calif. nies are now testing their devices in diabetics to deliver insulin without the need Drug clumps; cannot Fine drug aerosol enters blood for injections. enter blood vessels vessels readily, dispersing Until the mid-1990s, however, scien- throughout the body tists paid little attention to the aerosol Drug particles themselves. At that time, David A. Edwards, who was then a postdoctoral fellow in my lab (he is now a professor at Harvard University), began to think of ways to design better aerosol Blood vessels mists. He reasoned that by dramatically lowering the density of aerosol particles while increasing their size and porosity, he might reduce the tendency of the particles to aggregate, thus enabling them to enter the lungs through an air stream Alveoli produced by an extremely small, simple inhaler. Consider the difference between Lung bronchiole wet basketballs, for example, and wet grains of sand. The former have essentially no propensity for sticking together,

s the noted biologist Inder M. Verma of treat various cancers and liver disease. the Salk Institute for Biological Studies Specialized polymers are also being A in San Diego has stated, there are developed as gene therapy vectors by David three challenges in gene therapy: delivery, M. Lynn of the University of Wisconsin– delivery, delivery. To introduce a new gene Madison. Lynn, who was a postdoctoral into the body, scientists must condense the fellow in my laboratory at the corresponding DNA into small packages that Massachusetts of Technology, has can be taken up by a cell. But that is not all: synthesized sets, or libraries, of they must also protect the gene from the biodegradable cationic polymers called cell’s destructive enzymes, deliver it to the polyaminoesters. Along with Daniel nucleus and release it in active form. For Anderson, another postdoc in my lab, and years, scientists have harnessed viruses as David Putnam, who is now at Cornell vectors, Trojan horses that sneak foreign University, Lynn has made hundreds of such genes into cells. But even viruses that have polymers and has devised screening tests to been disabled carry risks, as the tragic death identify the most useful ones according to in 1999 of gene-therapy trial volunteer how readily they can bind to DNA, how Jesse Gelsinger made all too clear. soluble they are in blood serum and how well As researchers work to understand and they enter, or transfect, cells. Using this reduce the risks of viral vectors for gene method, the researchers have found a therapy, they are also devising alternative number of polymers that can transfect cells means for delivering genes that are based on more efficiently than the standard nonviral polymers or on fatty molecules called lipids. vectors lipofectamine and polyethylenimine. One interesting approach, developed by Fred E. Cohen of the University of Mark E. Davis of the California Institute of California at San Francisco has also Technology, involves polymers named employed the library approach. In cationic, or positively charged, B-cyclo- collaboration with Ronald Zuckerman of dextrins (CDs). Chiron in Emeryville, Calif., Cohen has Davis chose CDs because they are synthesized a new class of polymers called relatively nontoxic, do not elicit an immune peptoids or (more technically) cationic N- response and are soluble in water. He substituted glycine oligomers. Some of these originally intended to package DNA for gene can condense DNA into particles of between therapy into nanometer-size particles of CDs 50 and 100 nanometers in size that are alone but found that this simple combination capable of transfecting cells. was unstable when administered to animals. Lipids are also useful for delivering gene So Davis and a graduate student, Suzie therapy, according to Sung Wan Kim of the CIRCLET OF DNA, called a plasmid (top), Hwang Pun, came up with the idea of altering University of Utah. Kim wraps a particular must enter a cell and begin functioning to be an effective gene therapy. Most gene the surface of the CD particles by adding gene to be administered in a sheath of ) therapy tests in people have used viruses adamantane-conjugated polyethylene stearyl polylysine and then coats it with low- bottom to introduce genes into body cells, but they glycol (PEG). The modification generates density lipoprotein. In studies using rabbits, ( have raised safety questions. Researchers uniformly sized nanoparticles of CDs and he and his co-workers have employed this are now looking to package plasmids in ); MARK E. DAVIS AND

DNA that resist clumping into useless system to deliver the gene that encodes top cages of polymers (bottom) that are readily ( taken up by cells. aggregates with proteins in the blood serum. vascular endothelial growth factor (VEGF) to “Decorating” the surfaces of the particles heart muscle damaged by a lack of oxygen with the PEG compound also provided Davis (a condition called ischemia), as can occur and Pun with chemical hooks for attaching when blood vessels are blocked. Kim plans other molecules that could lead the particles to begin testing the approach next year in

to home in on, and deliver their genes to, patients with ischemic heart disease. The California Institute of Technology

specific types of cells. Insert Therapeutics hope is that the introduced VEGF gene will Custom Medical Stock Photo in Pasadena, Calif.—which Davis founded spur the growth of new blood vessels to bring and where Pun now works—is testing oxygen and nutrients to starved areas J. L. CARSON whether these targeted complexes can help of the heart muscle. —R.L. SUZIE HWANG PUN

56 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. “Smart” drug delivery systems would detect chemical signals in the body and release drugs in response to such signals. whereas the latter cling together readily. By making the aerosol particles larger, Edwards thought he could also de- CONTROLLING RELEASE crease their uptake by lung macrophages, HURDLE: Keeping the drug at a desired therapeutic level in the body while which tend to engulf smaller particles and avoiding the need for frequent administration to destroy drugs. Edwards and other scientists in our respective laboratories have SOLUTION: Implantable microchips with drug-filled reservoirs capped by gold shown that a single inhaled dose of insulin foil that can be dissolved by an electrical charge to release the drug at formulated in a large-particle aerosol can appropriate times last up to four days in the lungs of animals. This approach is now being tested SOME COMPANIES WORKING ON THE PROBLEM: in humans by Alkermes, a company based ChipRx, Lexington, Ky. in Cambridge, Mass.—in conjunction MicroCHIPS, Bedford, Mass. with pharmaceutical firms such as Eli Lil- ly—using several different drugs. IMPLANTABLE MICROCHIP Intelligent Microchips LOOKING FURTHER ahead, I see “smart” drug delivery systems as particularly exciting. These would detect chem- Gold foil cap ical signals in the body and release drugs Sealing layer in response to such signals, keeping the Drug reservoir concentration of a drug in the body at a desired therapeutic level. A number of years ago, while I was Drug release Gold foil watching a television program about how silicon chips for computers were made, I realized that the same technolo- the skin or into the spinal cord or brain into a computer at home, at a doctor’s of- gy might be applied to create smart sys- to deliver drugs ranging from pain med- fice, or in the hospital, providing a per- tems for administering drugs. In con- ications to chemotherapies against can- manent record of a patient’s drug history. junction with Michael J. Cima, an M.I.T. cer. Animal studies conducted by James ChipRx, a drug delivery company based expert in ceramics processing, I found an Anderson of Case Western Reserve Uni- in Lexington, Ky., is also developing im- undergraduate at the University of Mich- versity and his colleagues have shown plantable devices to sense the level of a igan at Ann Arbor, John T. Santini, Jr., that the materials in the microchips are drug in the body and administer appro- who agreed to explore the idea as a sum- quite biocompatible and unlikely to priate doses in response. It states that it is mer research project. Santini, who ended cause side effects. Chip-based systems, now preparing publications for scientif- up doing his Ph.D. at M.I.T., worked out which would include a small, wearable ic journals describing its devices. a way to create silicon microchips that power source, would be easy to use and We look forward to a day when any contain a number of wells that can be could keep an accurate record of how drug can be administered at the right loaded with drugs and covered with caps much drug a given patient is taking: data time, in the right dosage, anywhere in the of thin gold foil. Applying a one-volt elec- from the devices could be downloaded body with specificity and efficiency. trical signal to one or more of the wells dissolves the gold covers and releases the MORE TO EXPLORE drug. Santini is now president of Mi- Drug Delivery and Targeting. Robert Langer in Nature, Vol. 392 (Supplement), pages 5–10; croCHIPS in Bedford, Mass., which is April 30, 1998. Drug Delivery: Drugs on Target. Robert Langer in Science, Vol. 293, pages 58–59; currently developing these systems for July 6, 2001. testing in human patients. Ultrasound-Assisted Insulin Delivery and Noninvasive Glucose Sensing. Joseph Kost in Diabetes Microchips could be implanted under Technology and Therapeutics, Vol. 4, No. 4, pages 489–497; 2002. www.sciam.com SCIENTIFIC AMERICAN 57 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. Mount Etna’s Ferocious

By Tom Pfeiffer Translated by Alexander R. McBirney

VIOLENT ERUPTION of a flank vent on Mount Etna spews lava hundreds of meters into the sky in July 2001. Only 30 kilometers away is the city of Catania, the second largest on the Italian island of Sicily.

Future

Shooting molten rock more than 500 ing more dangerous. It is unlikely that meters into the air, Etna sent streams of Etna will explode like Mount Saint Hel- lava rushing down its northeastern and ens in the near future, but fierce eruptions southern flanks. The eruption was ac- may become more common. companied by hundreds of earthquakes measuring up to 4.3 on the Richter scale. Mountain of Fire As a huge plume of smoke and ash drift- THE NAME “ ETNA” is derived from ed across the Mediterranean Sea, resi- an old Indo-Germanic root meaning dents of Linguaglossa (the name means “burned” or “burning.” Extensive reports “tongues” of lava) tried to ward off the and legends record about 3,000 years of lava flows by parading a statue of their the volcano’s activity, but a reliable patron saint through the town’s streets. chronicle has been available only since the Perhaps because of divine interven- 17th century. Most of the earlier accounts LAVA FOUNTAIN erupts on Mount Etna’s southern tion, nobody was hurt and damage was are limited to particularly violent erup- flank on October 30, 2002. not widespread. But the episode was un- tions, such as those occurring in 122 B.C. nerving because it was so similar to an er- and A.D. 1169, 1329, 1536 and 1669. The volcano is more than 500,000 ratic eruption on the volcano’s southern During the eruption in 1669, an enor- years old. Remnants of its earliest erup- flank in the summer of 2001 that de- mous lava flow buried part of the city of tions are still preserved in nearby coastal stroyed parts of a tourist complex and Catania before pouring into the sea. regions in the form of pillow lavas, which threatened the town of Nicolosi. Some of With a surface area of approximately emerge underwater and do in fact look the lavas discharged in both events were 1,200 square kilometers, Etna is Europe’s like giant pillows. At first, a shield vol- of an unusual type last produced in large largest volcano [see map on page 62]. Its cano—so called because it resembles a amounts at the site about 15,000 years 3,340-meter-high peak is often covered shield placed face-up on the ground— ago. At that time, a series of catastroph- with snow. Only the upper 2,000 meters grew in a depression in the area where ic eruptions led to the collapse of one of consists of volcanic material; the moun- Etna now stands. Today a much steeper Etna’s predecessor volcanoes. tain rests on a base of sedimentary rock cone rests on the ancient shield volcano. The Sicilians living near Mount Etna beds. Blocks of this material are occasion- It consists of at least five generations of have long regarded the volcano as a rest- ally caught in the magma—the molten volcanic edifices that have piled up dur- less but relatively friendly neighbor. rock moving upward—and ejected at the ing the past 100,000 to 200,000 years, Though persistently active, Etna has not surface. Numerous blocks of white sand- each atop the remnants of its eroded or had a major explosive eruption—such as stone were blown out during the 2001 partly collapsed predecessor. The pre- the devastating 1980 event at Mount and 2002 eruptions. This phenomenon sent-day cone has been built in the past Saint Helens in Washington State—for occurs whenever magma must open new 5,000 to 8,000 years. Among Etna’s spe- hundreds of years. But now some re- paths for its ascent, as is usually the case cial features are the hundreds of small

searchers believe they have found evi- with lateral eruptions (those that occur on cinder cones scattered about its ﬂanks. ) dence that Etna is very gradually becom- the volcano’s ﬂanks). Each marks a lateral outbreak of magma. above One of the world’s most productive volcanoes, Etna has spewed about 30 mil- Overview/Etna’s Evolution lion cubic meters of igneous material ■ Long regarded as a relatively tame volcano, Mount Etna has rocked the Italian each year since 1970, with a peak erup- ); TOM PFEIFFER ( island of Sicily over the past two years. Eruptions on Etna’s flanks have produced tion rate of 300 cubic meters a second. lava flows that have destroyed tourist facilities and threatened nearby towns. Etna is also one of the most puzzling ■ Researchers believe that some of Etna’s molten rock is being generated by the volcanoes. Why has the magma that pro-

collision of two tectonic plates. If this hypothesis is correct, the volcano may duced it risen to the surface at this par- preceding pages eventually become much more violent and explosive. ticular spot, and why does it continue to

do so in such large quantities? The an- CORBIS (

60 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. swers should be found in the theory of plate tectonics, which posits that the earth’s outermost shell consists of about a dozen vast plates, each between about five and 150 kilometers thick. The plates constitute the planet’s crust and the up- permost part of the mantle. Like pieces of ice floating on the ocean, these plates drift independently, sometimes moving apart and at other times colliding. The 530 active volcanoes of the world are di- vided into three major types according to their positions on or between these plates. The first and most numerous type is found along the rift zones, where two plates are moving apart. The best examples are the long midocean ridges. Forces beneath the plates rip them apart along a fracture, and the separation causes an upwelling of hotter material from the underlying mantle. This material melts as it rises, producing basalt (the most com- MUSHROOM CLOUD of ash rises from Etna’s northeastern flank on October 28, 2002. mon kind of magma), which contains large amounts of iron and magnesium. ash. Such volcanoes typically have steep At the Crossroads The basaltic melt fills the space created by cones composed of alternating layers of ETNA, HOWEVER, cannot be assigned the separating plates, thus continuously loose airborne deposits and lava flows. to any of the three principal categories of adding new oceanic crust. Some of the best-known examples of volcanoes. It is located in a geologically The second type is located along the subduction-zone volcanoes rise along the complex area, which owes its current subduction zones, where two plates con- margins of the Pacific Ocean and in the form to tectonic processes that have been verge. Normally, a colder and heavier island arcs. This Ring of Fire includes active for the past 50 million to 60 million oceanic plate dives below a continental Mount Saint Helens, Unzen in Japan and years. An ocean basin that formerly ex- plate. The process that leads to the for- Pinatubo in the Philippines, all of which isted between Eurasia and the northward- mation of magma in this environment is have erupted in the past three decades. moving African continent was swallowed completely different: water and other flu- The third type of volcano develops in- to a large extent by the Eurasian plate. ids entrained with the sinking plate are re- dependently of the movements of the tec- About 100 million years ago two smaller leased under increasing pressure and tem- tonic plates and is found above hot spots plates, Iberia and Adria, split off from the perature, mainly at depths of about 100 caused by mantle plumes, currents of un- Eurasian and African plates because of kilometers. These fluids rise into the over- usually hot material that ascend by ther- enormous shearing stresses related to the lying, hotter mantle wedge and lower the mal convection from deep in the earth’s separation of North America from Eurasia melting temperature of the rocks. The re- mantle. As the mantle plumes approach (and the opening of the Atlantic Ocean). sulting magmas, which are more viscous the surface, decreasing pressure causes Mountain belts arose along the fronts and gas-rich than the basaltic melts of the them to produce melts that bore their way where the plates collided. Italy’s Apen- rift zones, contain less iron and magne- through the crust, creating a chain of hot- nines developed when the Iberian and sium and more silica and volatile compo- spot volcanoes. Most hot-spot volcanoes Adriatic plates met. During this process, nents (mainly water and carbon dioxide). produce highly fluid lava flows that build the Italian peninsula was rotated coun- These factors make the volcanoes in large, flat shield volcanoes, such as Mau- terclockwise by as much as 120 degrees subduction zones far more menacing than na Loa in Hawaii. to its current position. Today Etna is sit- volcanoes in rift zones. Because the viscous, gas-rich magma does not flow eas- TOM PFEIFFER has become very familiar with Mount Etna, photographing many of the vol- ily out of the earth, pressure builds up un- cano’s recent eruptions. He is a Ph.D. student in the department of earth sciences at the Uni- til the molten rock is ejected explosively. versity of Århus in Denmark. Pfeiffer has done research at the Hawaiian Volcano Observa- The sudden release of gases fragments tory at Kilauea volcano and the Vesuvius Observatory in Naples. His dissertation is about the magma into volcanic projectiles, in- the Minoan eruption on the Greek island of Santorini that devastated the eastern Mediter-

cluding bombs (rounded masses of lava), THE AUTHOR ranean region around 1645 B.C. An earlier version of this article appeared in the May 2002

TOM PFEIFFER lapilli (small stony or glassy pieces) and issue of Spektrum der Wissenschaft, Scientific American’s sister publication in Germany.

MOUNT ETNA is situated close to the juncture cone (dubbed Mongibello Recente). Recent Plate Adriatic Plate boundary of the Eurasian, African and Adriatic tectonic eruptions on Etna’s flanks seem to arise plates (left). The movements of these plates from a fissure that is not connected to the have fractured Sicily’s crust along fault volcano’s central feeding system. The two lines. A cross section of Etna (below) conduits appear to have separate magma Eurasian Plate reveals much of the volcano’s 500,000-year chambers about two to five kilometers below history. First, a flat shield volcano spread the volcano’s summit, although they share African across the sedimentary rock beds; then a the same magma source 50 to 100 Plate cone-shaped volcano rose above it. The kilometers farther down. (This part of the succeeding generations of volcanic cross section is not drawn to scale.) A contour Mount Etna edifices—named Rocca Capra, Trifoglietto map (bottom right) shows the locations of and Ellittico—piled atop their predecessors, the flank eruptions and lava flows that have Sicily forming the foundation for the present-day occurred in the past two years. —T.P. Summit Fault lines craters

Flank eruption

LAVA FLOWS DURING RECENT ERUPTIONS Central conduit Lateral Cones formed in 2001 Lava flows in 2001 fissure Cones formed in 2002 Lava flows in 2002

1,500 meters Northeast rift 2,000 meters

Pernicana fault Magma chambers 2,500 (two to five meters kilometers below 3,000 volcano) meters

Summit craters

GEOLOGICAL MODEL OF MOUNT ETNA Present-day cone Road Ellittico Predecessor Trifoglietto volcanoes Zafferana Rocca Capra First cone-shaped volcanoes Ancient shield volcano Magma source Sedimentary rock beds (50 to 100 kilometers Vertical scale exaggerated 150 percent below volcano) 0 3 kilometers DAVID FIERSTEIN

62 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. uated close to the junction of the African, Eurasian and Adriatic plates. Individual blocks from these plates have been su- perimposed and welded together on Sici- ly. Major tectonic faults cross the area around the volcano as a result of intense regional stresses within the crust. For a long time researchers believed that Etna’s position at the crossroads of these faults was the explanation for its volcanism. The presence of faults, however, accounts only for the ability of magma to reach the surface; it does not explain why the magma is produced in the first place. According to most theories, the prevailing forces in the Sicilian crust are similar to those in rift zones—extensional stresses that cause thinning of the crust and upwelling of the underlying mantle. But at Sicily the African and Eur- asian plates are colliding, so one would expect the stresses to be compressive rather than extensional. Moreover, only about 20 percent of the magma erupted at Etna has a chemical composition similar to that of a rift-zone volcano. Judging from its magma and pattern of activity, Etna is most similar to hot- ASH PLUME from Mount Etna is clearly visible in this image taken by NASA’s Terra satellite. spot volcanoes such as those in Hawaii. Recent theories suggest that it has devel- sure in the upper part of the magma col- these fountains rose as high as 1,200 me- oped above an active mantle plume, but umn allows the dissolved gases (mainly ters above the crater’s rim—a stunning no direct evidence for this plume has water and carbon dioxide) to escape. The height rarely observed at any volcano. been detected. So far scientists have been resulting bubbles rise within the magma To witness such an eruption from unable to explain all the characteristics of column and pop at the surface, throwing close range can be extremely dangerous, this enigmatic volcano. For example, out liquid and solid fragments. When the as I have learned from experience. In Feb- Etna is one of the few volcanoes in which level of the magma column is fairly deep ruary 2000, violent eruptions at Etna’s magma is almost continuously rising. Its inside the volcano, only gases and fine southeast crater were occurring at 12- or active periods can last for years or even ash particles reach the crater rim. When 24-hour intervals. On the evening of Feb- decades and are interrupted only by short it is closer to the surface, larger fragments ruary 15, while I was observing the crater intervals of quietness. This pattern im- (lapilli and bombs) are thrown out as from about 800 meters away with a plies the existence of two things: first, a well. In the rare cases when the magma group of spectators, a white cloud of constant flow of magma from the mantle column itself reaches the crater rim, the steam rose from the crater’s mouth. It to the deep and shallow magma reservoirs degassing magma pours over the rim or rapidly became thicker and denser. After beneath the volcano and, second, an open through a crack and forms a lava flow. a few minutes, the first red spots began conduit through which magma can rise. Besides lava flows, Etna produces an dancing above the crater, rising and falling In fact, the conduits between Etna’s mag- almost constant, rhythmic discharge of back into it. The explosions grew stronger, ma chambers and the summit craters steam, ash and molten rock. Known as a first slowly, then with breathtaking speed, seem to be very long lived structures. strombolian eruption (named after Strom- throwing bombs more than 1,000 meters

AP Photo Seismic investigations have shown that boli, a volcano on one of the Aeolian Is- above the rim. Soon the volcanic cone the rising magma produces little noise lands about 100 kilometers north of surrounding the crater was covered with and appears to move rather smoothly, Etna), this activity sometimes culminates glowing rocks. At the same time, a foun- without encountering major obstacles. in violent lava fountains jetting hundreds tain of lava started to rise from a fracture The kind of activity that prevails at of meters into the air. During the spec- on the ﬂank of the cone. Several other Etna depends primarily on the level of tacular series of eruptions at Etna’s fountains rose from the crater and formed

HO, NASA, TERRA SATELLITE magma inside its conduits. The low pres- southeast crater in the ﬁrst half of 2000, a roaring, golden curtain that illuminated

www.sciam.com SCIENTIFIC AMERICAN 63 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. ished 30 minutes after it began. In front Researchers soon determined that of us, the 300-meter-high cone still glowed two distinct eruptions were occurring si- red but was completely silent. multaneously. The opening of the fractures near Etna’s summit (between 2,700 Natural Air Polluter and 3,000 meters above sea level) was a ETNA’ S REPUTATION as a relatively continuation of the volcanic activity that friendly volcano stems mainly from the had been roiling the summit craters for fact that its lavas are very fluid. Such lavas years. But the eruptions at the lower frac- are easily ejected to the surface, unlike the tures (at elevations between 2,100 and viscous magmas produced by subduction- 2,500 meters) produced a more evolved zone volcanoes. But Etna’s magmas also type of magma that obviously had rested contain a great amount of gas, which can for a prolonged period in a separate make eruptions much more explosive. chamber, where it could change its chem- During a particularly violent phase, Etna ical composition. (A similar pattern was expels up to 20,000 tons of sulfur diox- also evident in the 2002 eruptions.) This ide a day, making the volcano one of na- second kind of magma included cen- ture’s worst air polluters. The high sulfur timeter-size crystals of the mineral am- content of Etna’s magma is hard to un- phibole, which is very rarely found in derstand; this characteristic is more typi- Etna’s lavas. Besides iron, magnesium and cal of subduction-zone volcanoes than of silica, amphibole incorporates water in its basaltic volcanoes. crystal structure. The mineral can form What is more, Etna’s composition in- only from a magma that contains suffi- dicates that the volcano has indeed ex- cient amounts of water. Obviously, two perienced major explosive eruptions sim- different plumbing systems of the volcano ilar in size to those of Pinatubo in 1991 were active at the same time: one associ- and Mount Saint Helens in 1980. Etna’s ated with the central, more or less con- last big explosion appears to have oc- stantly active conduit and the other with curred in 122 B.C. During that event, an independent conduit off to the side. STROMBOLIAN EXPLOSIONS illuminate newly more than one cubic kilometer of basaltic The magmas ejected through this sec- formed craters on Etna’s northern flank. lava erupted in a giant column loaded ond conduit were last produced in large with lapilli and ash. Deposits formed by quantities at Etna about 15,000 years the scene like daylight. Some larger bombs this eruption are up to two meters thick ago, when devastating eruptions caused crashed into the snow not far from us, but on Etna’s upper slopes and are still ex- the collapse of one of Etna’s predeces- we felt secure in our viewing position. The posed in some areas. In Catania, about sors, the Ellittico volcano. Is their reap- fountain was nearly vertical, and a strong 30 kilometers from the summit, the de- pearance a sign that a catastrophic ex- wind carried the mass of glowing lapilli posits are between 10 and 25 centimeters plosive eruption will happen in the near and ash gently away from us. thick. If such an event were to occur to- future? The answer depends on where Suddenly the lava fountain changed di- day, it would be a disaster. The roofs of Etna’s magmas come from. Identifying rection, sending a lateral outburst straight many houses in the area would collapse their origins can be tricky: analyzing the toward us. Just in time we reached the from the weight of the ash. erupted magma can be misleading, be- shelter of an abandoned mountain hut The unusual flank eruptions of 2001 cause the chemical composition of the with a thick concrete roof. A heavy rain and 2002 made it clear that Etna is not original melt often changes during its as- of incandescent stones fell around us; tame. In 2001 as many as five fractures cent through the crust. Geologists have lava bombs of all sizes tumbled down, opened on both sides of the mountain, learned, however, that surface lavas spraying thousands of sparks. Fortu- through which huge masses of lava start- sometimes contain crystals that preserve nately, our shelter was not hit by any- ed to pour. A new crater was born at an el- the composition of the original magma. thing large, although a two-meter-wide evation of 2,500 meters. Extremely active, If a crystal begins to form at an early bomb plunged into the snow nearby. Af- it spewed lava fountains and dense clouds stage in the life of a magma, it may inter an endless two minutes, the lava foun- of ash, growing within a few days to a clude minuscule droplets of the primitive tain rose vertically again and stayed in cone about 100 meters high. Especially melt and grow around them. These melt this position for another 10 minutes. spectacular were the giant magma bubbles inclusions are thus isolated from all sub- Then its supply of magma from below that rose within the new crater and deto- sequent chemical changes. seemed to be exhausted. The fountain nated with awesome power. Even at a dis- Analyzing such melt inclusions, collapsed as if it were sucked back into tance of several kilometers, the force of the though, is difficult. Until recently, almost

the crater. The entire spectacle was ﬁn- explosions rattled doors and windows. no suitable data were available for Etna. TOM PFEIFFER

64 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. In 1996 a French-Italian research team consisting of Pierre Schiano (Blaise Pascal University in France), Roberto Clocchiat- ti (National Center for Scientific Research in France), Luisa Ottolini (National Re- search Council in Italy) and Tiziana Busà (then at the University of Catania in Italy) began a comprehensive investigation of the magmas of Etna and neighboring volcanoes. The researchers looked for glassy inclusions in olivine crystals, which are among the first to form from a primitive melt. The tiny inclusions they discovered, each less than two tenths of a millimeter in diameter, were remelted on a heating plate, then quenched to create a homoge- neous glass. The team determined the LAVA FLOWS block roads and cut through forests on Mount Etna’s northern side in November 2002. chemical composition of the inclusions using a microprobe (which directs narrow boli and Vulcano. This island arc most ly migrated southward and come within beams of x-rays at a sample) and a sec- likely owes its existence to tectonic forces— reach of the plume beneath Etna. When ondary ion mass spectrometer (which em- specifically, the subduction of oceanic the rising plume passes by the edge of the ploys ion beams). crust from the Ionian Sea under the Cala- sinking slab, it creates the mix of magmas brian block (the southernmost part of the that emerges from the volcano. Changing Character Italian mainland). Schiano and Clocchiat- Etna’s activity has increased marked- THE SCIENTISTS PAID special atten- ti are convinced that the similarity of the ly since 1970, with more frequent eruption to the trace elements, such as cesium magmas is no coincidence. They believe tions and more volcanic material ejected. and barium, which are rare in igneous that Etna has two sources of magma: the Researchers cannot be certain, however, rocks. When a melt forms deep under- mantle plume that gave birth to the vol- whether this upsurge is caused by tecton- ground, the trace elements in the source cano and a second component that is iden- ic forces or by a fresh batch of magma ris- rock migrate almost completely to the tical to the magma feeding the Aeolian ing from the mantle. If Etna is indeed magma. Because their relative concentra- volcanoes. Furthermore, Etna’s youngest transforming into an explosive subduc- tions remain nearly unchanged, the trace magmas have the greatest amounts of this tion-zone volcano, the process will be a elements offer a geologic fingerprint of the second component. gradual one. As Schiano and Clocchiatti origin of the melt. The magmas that erupt- How does Etna produce its fiery mix emphasize, “The observed change [from ed at Etna more than about 100,000 years of magmas? One possibility is that the a hot-spot toward an island-arc volcano] ago had compositions similar to those two magmas form at different locations is taking place in geological time and not from the older, now extinct volcanoes of and mix somewhere within Etna’s plumb- in a human lifetime.” Thus, Etna is un- the Iblean Mountains in southern Sicily. ing system. This hypothesis would imply likely to experience a catastrophic explo- The trace-element patterns were also that the magma below the Aeolian Islands sive eruption soon. close to those found in magmas from hot- travels more than 100 kilometers along a But if the researchers’ hypothesis is spot volcanoes in Hawaii and the Azores. tectonic fault to Etna. It is considered correct, Etna’s eruptions will grow in- The early volcanism at Etna was appar- highly unlikely, though, that such an un- creasingly violent. Some tens of thou- ently fueled by a mantle plume, probably derground magma passage exists. Re- sands of years from now, Etna may well the same one that fed the Iblean volcanoes searchers think it is more probable that become as dangerous as Mount Saint Hel- about 100 kilometers to the south. the two magma sources are mixing. Ac- ens or Pinatubo. Fortunately, the Sicilians But the analysis of the younger mag- cording to this model, part of the sub- should have plenty of time to adapt to the mas (those that have been expelled with- ducted slab of the Ionian plate has slow- new situation. in the past 100,000 years) revealed a much different picture. They have large concen- MORE TO EXPLORE trations of trace elements such as cesium, Mount Etna: Anatomy of a Volcano. B. K. Chester, A. M. Duncan, J. E. Guest and C.R.J. Kilburn. potassium, rubidium and barium, but they Chapman and Hall, 1985. appeared to be depleted of elements such Transition of Mount Etna Lavas from a Mantle-Plume to an Island-Arc Magmatic Source. P. Schiano, R. Clocchiatti, L. Ottolini and T. Busà in Nature, Vol. 412, No. 6850, pages 900–904; as titanium and zirconium. Remarkably August 30, 2001. similar patterns are found at the Aeolian More information about Mount Etna, Stromboli and other volcanoes is available at

TOM PFEIFFER Island volcanoes, which include Strom- boris.vulcanoetna.com, www.stromboli.net and www.decadevolcano.net

www.sciam.com SCIENTIFIC AMERICAN 65 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. “It has not escaped our notice that the speciﬁc pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.” —James D. Watson and Francis H. C. Crick, Nature, April 25, 1953

“This structure has novel features which are of considerable biological interest” is one of science’s most famous understatements. James D. Watson and Francis H. C. Crick penned it for their report in the April 25, 1953, issue of Nature, in which they proposed the double helix model for the structure of DNA, the breakthrough that opened up our understanding of molecular biology and genetics. To mark the 50th anniversary, Scientific American Editor in Chief John Rennie recently spoke with Watson in his office at Cold Spring Harbor Laboratory on Long Island, where he was director for 25 years. Watson reflected on the origins of the double helix discovery, the current state of molecular biology, and controversies surrounding genetic science. (Because of poor health, Crick was not available for comment.) Hybrid Medical Animation Here is an abridged, edited version of that conversation. MIKE MEDICINE HORSE

www.sciam.com SCIENTIFIC AMERICAN 67 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. SCIENTIFIC AMERICAN: DNA is no longer just a scientific SA: You’ve said that you first became involved with research on entity. It’s erupted as this huge cultural phenomenon, as a DNA because of your interests in evolution and information. metaphor for our natures. It’s in our daily conversation, in art. When you were working on the double helix, did you foresee JW: [Physicist Erwin] Schrödinger probably wasn’t the first, DNA ever becoming this well known? but he was the first one I’d read to say that there must be a code of some kind that allowed molecules in cells to carry informa- JAMES WATSON: No, no, we couldn’t. Because no one had tion. By the time Schrödinger’s book [What Is Life? (1944)] ever sequenced DNA or amplified DNA. came out, a few people, such as [biologist J.B.S.] Haldane, were The famous Australian immunologist [Frank Macfarlane] making that connection between genes and proteins. Back in Burnet published this article in a medical journal that came out those days the amino acid sequence for a protein hadn’t been in 1961 or 1962, in which he said DNA and molecular biolo- worked out. You knew there was some sequence, but that’s all. gy will not have an influence on medicine. Because that’s only It was only our getting the DNA structure and [chemist Fred- possible when you can read the DNA. That’s why the Human erick] Sanger sequencing the first polypeptide [protein] chain Genome Project is so important. that let some air in. Back in 1953, all we wanted to do was find out how DNA provided the information and what the cellular machinery was SA: So would you say that your work was driven more by fas- for making proteins. That’s really all; we didn’t think about cination with that idea than by ambition? gene therapy. It took about 15 years before people began to think about that, around 1968—once restriction enzymes came JW: I was born curious. I would rather read economic history along and, soon after, DNA sequencing. than history, for example, because I liked explanations. And so if you wanted an explanation for life, it had to be about the molecular basis for life. I never thought there was a spiritual basis for life; I was very lucky to be brought up by a father who had no religious beliefs. I didn’t have that hang-up. My mother was nominally a Catholic, but that’s as far as it went.

SA: As we look back on the race for the double helix, it’s ob- vious that individual personalities strongly influenced the specifics of who found it first and how. And yet the discovery at roughly that time also seems to have been inevitable. There were so many of you who were so close—you and Crick, Linus Pauling of the California Institute of Technology, Maurice Wilkins and Rosalind Franklin of King’s College. If you and Crick had not made the discovery when you did—

JW: I can’t believe a year would have passed.

SA: There has always been controversy about Wilkins showing

you Franklin’s crystallography images without her permission, )

giving you and Crick an important clue to DNA’s structure. In left

retrospect, would it have been more appropriate for the Nobel and committee to have given the prize to her, along with you and Crick, rather than to Wilkins? preceding page JW: I think not. Wilkins gave us the crystalline photograph of ( the A form, and she gave us the B form. So you could have said that in an ideal, perfect society, they would have gotten the

I think there’s something in me of that same weakness that is so apparent in Cold Spring Harbor Laboratory John McEnroe. I just can’t sit while

people are saying nonsense. MIRIAM CHUA

chemistry prize, and Crick and I would have gotten the biology prize. That would have been a nice way to honor the four of us. But no one thought that way. We’re very famous because DNA is very famous. If Ros- alind had talked to Francis starting in 1951, shared her data with him, she would have solved that structure. And then she would have been the famous one.

SA: In a century, we went from rediscovering Mendel’s laws and identifying chromosomes as agents of heredity to having the human genome largely worked out. Finding the double helix drops neatly in the middle of that span. How much, with respect to DNA, is left for us to do? Are there still great discoveries to be made, or is it all just ﬁlling in details? WATSON and Francis Crick (right), 1953

JW: The major problem, I think, is chromatin [the dynamic roe. I just can’t sit while people are saying nonsense in a meet- complex of DNA and histone proteins that makes up chro- ing without saying it’s nonsense! mosomes]. What determines whether a given piece of DNA along the chromosome is functioning, since it’s covered with SA: On the subject of politics, many gene-related issues are in the histones? You can inherit something beyond the DNA se- the public arena these days: genetically engineered foods, quence. That’s where the real excitement of genetics is now. cloning, DNA fingerprinting and so on. How much confidence And it seems to be moving pretty fast. You don’t really do you have in the political supervision of these? want to make a guess, but I’d guess that over these next 10 years, the field will be pretty played out. A lot of very good peo- JW: I think they’re so contentious that the state shouldn’t en- ple are working on it. We have the tools. At some stage, the ba- ter in. Yes, I would just stay out of it, the way [government] sic principles of genetics will be known in terms of gene func- should stay out of abortion. Reproductive decisions should be tioning, and then we’ll be able to apply that more to problems made by women, not the state. such as how the brain works. I mean, cloning now is the issue. But the first clone is not like the first nuclear bomb going off. It’s not going to hurt anyone! SA: If you were starting out as a researcher now— I know a famous French scientist who never had children because there was madness in his family. He didn’t want to JW: I’d be working on something about connections between take a chance on more madness. That’s what I mean. Cloning genes and behavior. You can find genes for behaviors, but that might mean you would know there wasn’t going to be any doesn’t tell you how the brain works. My first scientific inter- more madness. I think the paramount concern should be the est was in how birds migrated. Until you know how the bird rights of the family, as opposed to the rights of the state. brain works, you’re not going to know how genes can tell that People say, “Well, these would be designer babies,” and I say, bird where to migrate. Because, you know, that mother bird isn’t “Well, what’s wrong with designer clothes?” If you could just telling the young one where to go! So it’s got to be inherited. say, “My baby’s not going to have asthma,” wouldn’t that be There are lots of other big behavioral things [to solve]. nice? What’s wrong with therapeutic cloning? Who’s being hurt? Some people say they’re mystified that men can like men, but If you thought every plant was the product of a god who I say, “It’s just as mysterious as why men like women!” put it there for a purpose, you could say that you shouldn’t These things are so difficult. Francis insists that brain re- change it. But America isn’t what it was like when the Pilgrims search doesn’t have [the equivalent of] a DNA molecule. It came here. We’ve changed everything. We’ve never tried to re- doesn’t have a central thing from which everything else flows. spect the past, we’ve tried to improve on it. And I think any de-

Photo Researchers, Inc. sire to stop people from improving things would be against the SA: You have a reputation for being outspoken, and you get crit- human spirit. icized for it. Do you have any regrets about things you’ve said? An extended version of this conversation and a list of JW: Occasionally. I think there’s something in me of that same suggested readings is available at www.sciam.com. Watson’s

A. BARRINGTON BROWN weakness that is so apparent in [tennis champion] John McEn- latest book is DNA: The Secret of Life (Knopf, 2003).

www.sciam.com SCIENTIFIC AMERICAN 69 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. In the past year scientists have been forced to reconsider how they identify life in the most ancient ISUA, GREENLAND (opposite page), is home to rocks rocks on earth— harboring well-accepted evidence that living cells existed on earth more than 3.7 billion years ago, and elsewhere only several million years after the planet itself formed. But other extremely old finds in Greenland and Australia—including microscopic squiggles in the solar system thought to be fossil cells (above)—have recently been challenged. uestioning Qthe OldestSignsof By Sarah Simpson Life 70 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. Prehistoric creatures left seemingly endless proof of their existence fossilized in age-old time when simple inorganic molecules ever be sure of correctly identifying prim- rocks. Monstrous thighbones of lumber- first self-replicated and began selectively itive life on earth—or elsewhere in the so- ing dinosaurs that drowned in flooded interacting with their environment, defin- lar system. “If we can’t get it right on rivers now lie encased in sandy mudstone. ing life’s earliest moments. By 1996 new earth, we can’t get it right on Mars,” says Jagged fronds of tropical ferns once grow- techniques for measuring slight variations paleontologist Bruce Runnegar of the ing in muddy swamps are pressed be- in the chemical makeup of carbon sam- University of California at Los Angeles. tween jet-black layers of coal. Squiggly ples seemed to solidify previous hints that That’s a point that space scientists are worm burrows, excavated within a slimy life existed at least 365 million years ear- sure to keep in mind when evaluating seabed, lace steel-gray limestone. These lier. That same year the stunning an- Martian rocks slated to be inspected by signs of life are unmistakably distinct nouncement that a meteorite found in two NASA rovers early next year. from their stony tombs. But the more an- Antarctica was carrying 3.9-billion-year- cient the creature, the more obscure its old biosignatures from Mars further en- To Hell and Back grave. ergized scientists, who grew more confi- THE MOST ANCIENT—and easily the Before life began walking, slithering dent in their ability to detect past life from most controversial—evidence of life on or putting down roots, nothing much faint traces in rocks. the Blue Planet turned up seven years ago more than solitary microscopic cells pop- But the uncontested glory did not last. on a tiny nubbin of land at the southwest ulated the globe. Virtually all traces of Evidence from the Martian meteorite corner of Greenland’s cold and barren is- those that lived before about 2.5 billion came under fire almost immediately, and land of Akilia. The island, which squats years ago—a period known as the Ar- only one life sign from Mars still clamors 30 kilometers south of the capital, Nuuk, chean eon—have since become nearly in- for acceptance [see box on page 76]. In extends a mere two kilometers across at distinguishable from the rocks that en- early 2002 confidence over the widely ac- widest reach; a hiker can traverse the tomb them. Millions of brutal years of cepted views on earthly evidence experi- ground in question in five minutes. There, burial and resurfacing, akin to repeated enced a similar meltdown. A flurry of re- underneath thick patches of arctic moss pressure cooking, permitted very few fos- search has cast serious doubt on interpre- and lichens, all-important bands of milky, silized cells to survive in rocks accessible tations of the earth’s two oldest geologic quartz-rich rock gleam among the darker at the earth’s surface today. Often geolo- records of life, in Greenland and Aus- volcanic slabs surrounding them. Using ) gists must instead rely on other signs of tralia. Some new evaluations of the geol- radioactive elements found only in vol- life, or biosignatures—including rather ogy suggest that the rocks formed in en- canic minerals, scientists have dated one subtle ones, such as smudges of carbon vironments where life never could have nearby slab to a whopping 3.83 billion preceding page with skewed chemical compositions thrived. Others question whether lifeless years ago, ranking it among the oldest (

unique to biology. chemistry might have been able to mimic rocks preserved on the earth’s surface to- Corbis A decade ago high-powered micro- the special traces of carbon or even the day. And based on the position of the scopes enabled geologists to detect ap- shapes of microscopic fossils—rendering gleaming white rock (which contains no parent fossils in earthly rocks an aston- these clues useless as biosignatures. datable minerals), many geologists say

ishing 3.465 billion years old—as close as The revisionist analyses are fueling an that the white material is even older. ); JAMES L. AMOS tangible fossils may ever take us to the ongoing debate over how anyone can Akilia’s stark landscape gives the im- page 70

pression that its rocks have looked this ( way ever since their primordial origins. Overview/Early Life But the earth is a dynamic place. These ■ Many traces of the earth’s most ancient microscopic life—so-called outcrops—like most from the Archean biosignatures—are subtle and encased in rocks. Apparent biosignatures become eon—have suffered one of the most tor- most convincing as signs of life when geologists can confirm that the host rocks turous geologic processes that the earth formed in a biologically friendly environment, such as a shallow sea. has to offer: metamorphism. For 85 per- ■ Several biosignatures can be mimicked by nonbiological chemical reactions that cent of the planet’s lifetime, these rocks occur at high temperatures and pressures—reactions often experienced by were buried, twisted, folded or pumped deeply buried rocks or those that harden from a molten state. full of ﬂuids; they were plunged to hellish University of California, Los Angeles ■ The ambiguity surrounding the origins of apparent biosignatures demonstrates depths nearly 70 kilometers underground that accurate interpretations of the geology are key to any search for signs of and baked at 700 degrees Celsius before very ancient life, be it here on earth, on Mars or beyond. returning to the surface during at least

two different episodes of uplift. If any of J. WILLIAM SCHOPF

72 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. Subsequently, Fedo and geochronol- ogist Martin J. Whitehouse of the Swe- dish Museum of Natural History in Stockholm returned to Akilia to make their own maps and chemical analyses. Their verdict, which they published last spring, was that the quartz-rich rocks that Mojzsis and others were calling old sediments were actually the progeny of igneous rocks that had endured a particular metamorphic process known to create graphite from nonbiological sources of carbon. Fedo and Whitehouse insisted WHITE STRIPES in this rocky outcrop at the southern tip of Greenland’s tiny island of Akilia hide flecks that the graphite’s light carbon signature of carbon that were initially hailed as a signature of life older than 3.8 billion years. might have to be explained by some process unrelated to biology. It is wrong, these rocks are the relics of the floor of an compelling evidence for the oldest known Fedo asserts, to believe that inorganic re- ocean once teeming with microscopic life on earth. This conclusion had an ad- actions cannot mimic light carbon signa- creatures, it could well be impossible to ditional implication—that life got its start tures just because they haven’t been find traces of those organisms still intact. in a hostile period when devastating me- proved to do that so far. Yet in 1996 geochemist Stephen J. teorite impacts were boiling off the Mojzsis, now at the University of Col- oceans and turning the earth’s atmo- Geology Is Everything orado at Boulder, glimpsed a suggestion sphere into a scorching mist of vaporized ENORMOUSLY COMPLICATED geol- of life inside that tortured white stone. rock for millennia on end. Indeed, many ogy is the reason that Mojzsis, Fedo and Through the probing eye of a scanning scientists hailed Mojzsis’s discovery as the a slew of other investigators disagree electron microscope, he discerned black key that would unlock a virtually un- about Akilia. It is also the reason that field specks of graphite, a pure-carbon miner- known era of earth history, says geologist geologist Minik T. Rosing of the Univer- al that sometimes forms when organic Christopher M. Fedo, now at George sity of Copenhagen’s Geological Museum matter is heated. He also noted that tough Washington University. calls Akilia “utterly uninteresting.” No crystals of apatite encasing the graphite A year later, in 1997, Fedo accompa- combination of geologists can agree on probably sheltered it from the harshest nied Mojzsis and several other geologists the history of the rocks, he says, and so metamorphic transformations. to Akilia. Fedo recalls that at first it felt “we might never be able to resolve the But what convinced Mojzsis were the “like visiting hallowed ground.” But al- problem.” And that’s from a Greenland uniquely skewed ratios of isotopes in the most immediately the two young re- native who has spent more than 20 years two dozen specks he analyzed in more de- searchers began seeing different pictures studying the icy island’s geology. tail. Each was diagnostically enriched in of the past—and different explanations But many investigators have not let go the lightest and most common isotope of for what the light carbon signal really of settling the debate at Akilia. Indeed, carbon: carbon 12. Living organisms are means. From the makeup and structural Akilia is near the top of Bruce Runnegar’s frugal. So when they use carbon dioxide relation of the rocks, Mojzsis and his col- agenda as the new director of NASA’s As- to fuel their activities, they exploit the leagues had inferred that the graphite- trobiology Institute, a consortium of 15 light carbon isotope more efficiently than bearing rock originated in a biologically research teams across the U.S. dedicated they do carbon 13, which is notably heav- friendly environment: an ocean basin to pursuing evidence for the origin and ier because of an extra neutron in each where sand and other particles, including evolution of life on earth and beyond with atom’s nucleus. This preference leaves the cells of marine organisms, formed lay- an annual budget approaching $20 mil- them with a surplus of carbon 12 atoms— ers of quartz-rich sedimentary rock. On lion. “Within a year or so we plan to take roughly 2 to 3 percent more than exists in seeing the rocks for himself, Fedo, who the people who really know the rocks and carbon dioxide dissolved in the ocean. had just spent a year mapping Archean get some sort of consensus on what we’re This light carbon signature had been rocks in Zimbabwe, became extremely sampling in the field so that everybody gaining support as an uncontestable skeptical. He knew that igneous rocks— knows what everybody else is talking

George Washington University marker of life for almost 60 years as re- those solidiﬁed from hot magma—can about,” he says. searchers published thousands of similar look sedimentary, and vice versa, once Yet Rosing and other researchers—in- measurements from younger rocks. they have lost or gained key minerals dur- cluding paleontologist J. William Schopf Therefore, when Mojzsis’s graphite sam- ing metamorphism. “If we’re going to un- of U.C.L.A.—point out that even if scien- ples clustered around 3.7 percent, it made derstand life, we’d better understand ge- tists can agree that the rocks at Akilia are

CHRISTOPHER M. FEDO perfect sense for him to declare them ology,” Fedo says. former sediments, they still won’t be able

www.sciam.com SCIENTIFIC AMERICAN 73 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. to prove where or when the carbon orig- apatite. “There really is no good way, in recently detected the light carbon biosig- inated. They insist that light carbon, and my opinion, to go from [the measured] nature in rocks that he argues experi- indeed graphite, in such highly metamor- value back to what the original values enced a mere migraine compared with phosed rocks can only suggest the possi- were,” Schopf says. “There’s a big differ- Akilia’s hellish past. This pocket of rela- bility of life. By itself, it cannot constitute ence between knowing it and having a tively gentle metamorphism was not easy proof. When sediments are pressure- hint.” to ﬁnd. Isua’s four-kilometer-wide belt of cooked, ﬂuids might carry in carbon from Akilia’s limelight has diverted atten- Archean rocks stretches 35 kilometers other, younger sources. Also, the carbon tion from a much more convincing hint along the western edge of the bluish-gray bonds of any organic matter within them of early life that exists about 180 kilo- monolith of the Greenland ice cap. The start to break and can be reset, even if the meters northeast of that island, in a part distinctive shimmer of the rocks and their carbon is sheltered by tougher crystals of of Greenland called Isua. There Rosing marble-size crystals of red garnet, black Biosignatures at a Glance BEFORE PLANTS AND ANIMALS AROSE, single-celled microbes populated the earth. Scientists gather physical signs of these primitive organisms by combing ancient rocks for subtle traces of their existence, called biosignatures. But such finds can be questioned as evidence for life if their presence can be plausibly explained by nonbiological processes—as in the disputes described below. —S.S.

LIGHT CARBON LIGHT SULFUR DEFINITION: Carbon having a higher ratio of carbon 12 to carbon DEFINITION: Sulfur having a higher ratio of sulfur 32 to sulfur 13 than occurs in nonbiological materials; the higher ratio 34 than does sulfur that has not been processed by the reflects organisms’ preference for using carbon 12 as microscopic organisms that use this element as a source they convert carbon dioxide into cellular material. of energy. OLDEST DISCOVERY: Tiny specks of carbon found in OLDEST DISCOVERY: Flecks of the iron-sulfide mineral Akilia, Greenland, in rocks more than 3.8 billion years pyrite within 3.5-billion-year-old rocks from old. Recent research contradicts assertions that the host northwestern Australia. Some researchers question rocks came from an environment that could have supported whether the spiky gray crystals (right) that harbor the life. The debate leaves carbon (black dots, left) in rocks that pyrite truly formed in an environment that could have sustained formed more than 3.7 billion years ago in Isua, Greenland, as the life. Records of this biosignature become unambiguous by about oldest uncontested relic of life on earth. 2.5 billion years ago.

STROMATOLITES MOLECULAR FOSSILS DEFINITION: Layered, domelike formations constructed DEFINITION: Complex organic molecules resembling those by colonies of microbes. in living cells today. OLDEST DISCOVERY: Fossilized mounds discovered in OLDEST DISCOVERY: Hydrocarbons found in Australian northwestern Australia and dating to about 3.5 billion rocks some 2.7 billion years old. These molecules, years ago; these are the oldest known macroscopic derived from fossilized cell membranes, are the oldest representatives of life on earth (left). Most other undisputed evidence for eukaryotic cells (those containing stromatolites of this age are disputed as evidence for life a true nucleus) and for oxygen-producing cyanobacteria, because their simpler structures strongly resemble mineral possibly even the lineage that led to Eoentophysalis (right) layers that can be produced nonbiologically. 700 million years later.

MICROFOSSILS BIOLOGICAL MINERALS DEFINITION: Remains of once living cells. DEFINITION: Mineral grains produced by living cells. OLDEST DISCOVERY: Microscopic, carbon-rich squiggles OLDEST DISCOVERY: Unique forms of the magnetic (left) found in 3.5-billion-year-old rocks in northwestern mineral magnetite (right)—nearly identical to those Australia. These finds were originally interpreted as known to occur in certain modern bacteria on earth— remnants of ancient microbes, but recent work found in the Martian meteorite ALH84001. The Martian suggests lifeless chemistry could have created them. minerals are thought to be 3.9 billion years old; similar Younger microfossils, including a two-billion-year-old magnetite crystals have been detected in Australian rocks cyanobacterium from Canada, are widely accepted. nearly two billion years old. Both finds remain in question.

74 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. hornblende and sage-green diopside in most places attest to metamorphic tor- tures nearly as intense as those experienced at Akilia. “I didn’t go there to look for life, and I’ve always been skeptical about it,” says Rosing, who initially visited Isua to understand how hot ﬂuids transform the rocks. Since his ﬁrst research visit in 1980, he has traipsed repeatedly among cari- bou, white polar hare and ptarmigan in this remote area—accessible only by heli- copter—for one to three months at a shot. This intensive examination eventually enabled him to set aside rocks that were igneous or otherwise too complicated to harbor clear signs of life. Then, in 1999, he described a promising outcrop of old sediments at Isua’s western edge that other geologists agree must be older than 3.7

), billion years, making them potentially as old as Akilia’s. And that’s where he found ), the light carbon biosignature. The relatively undisturbed geology in

molecular fossils this part of Isua revealed important de- ( stromatolites ( tails about the sedimentary environment MARS-LIKE LANDSCAPE of northwestern Australia’s Pilbara region is the source of 3.5-billion-year-old that were simply impossible to decipher microscopic structures that some interpret as fossilized strings of ancient cells. at Akilia. The light carbon was tied up in layers of clay, which would have trapped Surf or Sizzle? among silica-tipped spines of spinifex McGill University organic particles when they settled to the OF ALL POTENTIAL biosignatures, grass or the occasional roadhouse mark-

University of Missouri bottom of an ocean. The carbon is also what pleases scientists most is a bona ﬁde ing the spot where one dirt track meets abundant in the rocks, and it persists fossil of an organism’s body, even if it is another, the dusty, low hills of north- through a thick pile of ancient sediments only one or two cells in size. In this cate- western Australia might be mistaken for ), H. J. HOFMANN Corbis ), TIM LYONS that represents as much as a million or gory, Australia’s timeless landscape holds Mars. Near Marble Bar, a tiny watering more years of slow deposition. Every day, most of the records. Uncontestable mi- hole in this sublime sea of red, geologists light sulfur

( every night, for all that time, carbon with crofossils—including those of oxygen- long ago described the Apex chert—the ﬁ- light carbon ( exactly the same composition of that in producing cyanobacteria—exist in rocks nal home of Schopf’s tiny, famous fos- present-day microorganisms rained down about two billion years old. And con- sils—as a mixture of sand and small peb- to the bottom of a deep ocean, Rosing vincing examples of so-called molecular bles once churned by waves along a shal- explains. fossils—relics of complex organic mole- low seaway ﬂanked by volcanoes. The ); THIS PAGE: PENNY TWEEDIE So far no one has seriously challenged cules that were once fatty constituents of chert (which, like the graphite-bearing

University of Washington his basic interpretations, and he has been cell membranes—turned up three years rocks of Greenland, cannot be dated di- working to characterize the microbes ago in rocks 2.7 billion years old. But nei- rectly) is conveniently sandwiched be- that might have produced light carbon. ther of these exciting ﬁnds pushed back tween two lava ﬂows, which have been biological minerals

( “That’s what everyone thinks is the best the fossil evidence as far as the pioneering dated precisely at 3.46 billion and 3.47 ), ROGER BUICK bet for evidence of biology in Greenland,” work of Schopf, who, after devoting three billion years old. Of the half a dozen Runnegar says. decades of study to ancient microscopic claims of Archean microfossils—includ- Geological Museum, University of Copenhagen But even the best evidence in Green- fossils, launched a new wave of early-life ing ones from four locations in South microfossils (

Lockheed Martin land offers only a solitary sign of life. research in 1993. Africa—this age made Schopf’s the oldest. Surely a multiplicity of clues from a single As in Greenland, the oldest signs of Further analysis would reveal that his U.C.L.A. site would be even more convincing. That life in the land Down Under are exposed cache, if truly biological, was also the was precisely the strength of Schopf’s in a remote, desolate area—an ancient most diverse, with 11 new species of mi- landmark interpretation of rocks on the landscape about 1,200 kilometers north croorganisms identiﬁed. other side of the world, one that went un- of Australia’s west coast port of Perth. If According to Schopf, the chert con- KATHIE L. THOMAS-KEPRTA OPPOSITE PAGE: MINIK T. ROSING J. WILLIAM SCHOPF contested for nearly a decade. it weren’t for the wallabies hopping tained telltale smudges of graphite that he

www.sciam.com SCIENTIFIC AMERICAN 75 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. calls threadlike strands of once living a reinterpretation of the local geology— ing, however, was Brasier’s suggestion cells. His biological interpretation of these and of the fossils themselves. In March that many of the microscopic structures smudges was backed by the chert’s dis- micropaleontologist Martin D. Brasier of that evoke life for Schopf may be nothing tinct enrichment in light carbon and the the University of Oxford and seven of his more than lifeless artifacts. nearby presence of fossilized stromato- colleagues published the first robust re- Today Schopf admits that it was a lites, mineralized mounds of bacterial analysis of Schopf’s 1993 conclusions. mistake to rely on the geologic mapping mats that serve as the only sign of Arche- Among several challenges, Brasier assert- of others in the construction of his origi- an life visible to the naked eye. Based ed that the chert harboring the presumed nal story, conceding, albeit reluctantly, on this trio of evidence, everything from fossils was not deposited on the sunny that his famed fossils may not have been textbooks to television, even the Guinness floor of a shallow sea but rather deep photosynthesizers. Instead they may have Book of World Records, touted this land- within the dark subsurface plumbing of been the forebears of heat-loving bacte- mark finding as the earth’s oldest fossil seafloor hot springs. This distinction is ria that color the steamy geyser pools evidence for life. critical because Schopf had proposed that in Yellowstone National Park and popu- But early last year Schopf’s celebrated many of his fossils may have been light- late submarine volcanoes. Schopf has revision of the cradle of life was upended by loving cyanobacteria. Even more damag- cently reevaluated the carbon smudges using a technique known as Raman imagery, which employed scattered light to probe their internal three-dimensional Martian Magnets structures. The results indicate that many of the structures in question look like cell walls. PULLING CONVINCING SIGNS OF LIFE out of a single space Still, Brasier asserts that the light car- rock isn’t easy. But one of the last surviving claims that bon enrichments may well be able to biosignatures endured meteorite ALH84001’s trip from Mars form through lifeless chemical reac- METEORITE ALH84001 has weathered a recent barrage of criticism. tions—much as Fedo and others have ar- hit Antarctica 13,000 For the past seven years microscopist Kathie L. years ago. gued could have occurred at Akilia. Lit- Thomas-Keprta of Lockheed Martin in Houston and her tle definitive research has been done in colleagues have kept alive the idea that minuscule grains of the mineral magnetite this area, but a handful of experiments within the potato-size meteorite—bits widely accepted to have formed on Mars some do suggest that the right combination of 3.9 billion years ago—are indistinguishable from the tiny magnets made by some metals and other chemicals—like those ) aquatic bacteria on earth. abundant in seafloor hot springs—might

Skeptical researchers have pointed out that, as is true of certain putative ignite reactions that could mimic biolo- bottom biosignatures on earth, a lifeless chemical process could have created the lifelike gy’s preference for the light isotope of material, in this case a heat-induced transformation of iron-rich minerals during a carbon. And although Brasier does admit collision the rock suffered while still on Mars. But such an impact would have created that some of the carbon could represent magnetite with impurities (such as magnesium and manganese), Thomas-Keprta scattered remains of microbes, he insists notes, and the grains she calls biosignatures are 100 percent pure—a finding she that “you must falsify [nonbiological] and her colleagues recently confirmed with new three-dimensional tomography origins for these materials before you ac- scans of the Martian magnetite. cept biological ones.” In addition to the lack of chemical impurities, about 25 percent of the magnetite The same policy must be applied, in ALH84001 shares at least five other distinct characteristics with magnetite Brasier and others would argue, to an- ); NASA AND THE HUBBLE HERITAGE TEAM ( — —

made by the bacterial strain MV-1 here on earth. The Martian and MV-1 other biosignature light sulfur pre- top magnetite grains are in the same size range, lack significant structural served within 3.47-billion-year-old Aus- ( defects and share an unusual elongated crystal shape that strengthens tralian rocks that sit a two-hour, back- the mineral’s magnetic properties, for instance. If any single criterion is breaking car ride northeast of the con- absent from a Martian grain, it is excluded from further consideration as a troversial Apex chert. Sulfur-rich rocks

possible biosignature. The test is so stringent that nearly one third of the from the ironically named North Pole dis- www.setileague.org MARS bacterial crystals would fail to pass the test, Thomas-Keprta points out. trict contain a surplus of sulfur 32 (rela- The new evidence makes her almost certain that the tiny magnets are true signs tive to heavier sulfur 34) that is charac- of past life on Mars, but many other scientists remain unconvinced. Even Thomas- teristic of waste materials produced by Keprta says she won’t be satisfied with finding only one likely trace. “Defining a bacteria known to use sulfur as an energy biosignature is almost as difficult as defining life itself,” she admits. In the next year source. Light sulfur signatures, like those she and her colleagues will begin to scour the meteorite for a particular iron sulfide of carbon, unambiguously record life mineral that bacteria on earth are known to produce. —S.S. over much of the earth’s history. But in

these very old rocks in western Australia, SETI LEAGUE, USED BY PERMISSION

76 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. ling a search for past life. “When you consider the fact that field geologists have been crawling over the earth for 200 years and are still having problems [agreeing on reliable biosignatures], we’re way far away from being able to do a credible search for biosignatures on Mars,” says planetary scientist Steven W. Squyres of Cornell University. Since 1997 Squyres has been working as chief scientist for NASA’s upcoming Mars landing missions, which will scour the planet’s surface for hints that its past environment might have been biological- STROMATOLITES, towering structures built by colonies of microorganisms, live today in such places ly friendly. Two remote-controlled, ro- as Shark Bay, about midway along the western coast of Australia. Ancient versions dating to about botic geologists, called the Mars Explo- 3.5 billion years ago are among the few putative signs of life that old that are still largely unchallenged. ration Rovers, are scheduled for launch in the controversy is the same: Did the rocks Africa’s Transvaal Basin are just a tad late May and June and should begin their form in low-temperature environments younger and, some would argue, much fieldwork on the Red Planet in January inhabited by bacteria or in higher-tem- less controversial. Although many scien- 2004. The landing sites, to be announced perature locales where nonbiological re- tists quibble over the details, the great an- sometime this month, will target spots actions could have mimicked the bacter- tiquity of life is generally accepted. where orbiting spacecraft have discovered ial isotope patterns? Australian geologist Perhaps the most important conclu- tantalizing hints that liquid water—a re- Roger Buick of the University of Wash- sion that has crystallized from these ar- quirement for all known forms of life— ington and his collaborators argue the guments is this: whether you are investi- once existed. former, stating that sulfur-bearing crys- gating ancient rocks on earth or potato- As experiences from Greenland and tals formed in an evaporating lagoon. size meteorites from other planets, don’t Australia illustrate, it is difficult to find But not everyone, most notably Run- count on a single smoking gun to be your readable records here on earth because negar, agrees with this interpretation of proof of life. That conclusion has serious the constant motion of tectonic plates the region’s geology. implications for further hunts for early have so chewed them up over the past Despite the controversies, Schopf life on earth and for how future evidence four billion years. But because such a maintains his basic position. He counters from Mars is interpreted. Brasier cautions global process may never have existed on that although an individual biosignature that without having “the criteria for the Mars, researchers predict that its surface can be cast in an uncertain light, the un- detection of early life clear in our minds has remained intact—except for a few me- certainty does not render the evidence before we have a robotic or manned mis- teorite impacts—during that same period. useless. A suite of biosignatures from a sion to Mars ...we will end up having Squyres notes the irony: “If life did come single location—even if disputable when profitless debates that may simply de- to being on Mars, evidence for it might be viewed individually—packs a powerful moralize the scientific community.” much easier to find.” punch. He is fond of saying, “If it looks NASA scientists share that concern, like life, has the ecology of life, has the iso- which is why they are determined to de- Sarah Simpson is a contributing editor topes of life and fits with all other evi- cipher the geology of Mars before tack- at Scientific American. dence of life, then most likely it’s life.” MORE TO EXPLORE Earth and Beyond Evidence for Life on Earth before 3,800 Million Years Ago. Stephen J. Mojzsis et al. in Nature, Vol. 384, pages 55–59; November 7, 1996. STILL, IN THE END, the interpretations 13 of the oldest rocks in both Greenland and C-Depleted Carbon Microparticles in >3700-Ma Sea-Floor Sedimentary Rocks from West Greenland. Minik T. Rosing in Science, Vol. 283, pages 674–676; January 29, 1999. Australia are unavoidably complicated by Cradle of Life: The Discovery of Earth’s Earliest Fossils. J. William Schopf. Princeton University the possibilities of both biological and Press, 2001. nonbiological origins. Lest you worry Questioning the Evidence for Earth’s Oldest Fossils. Martin D. Brasier et al. in Nature, Vol. 416, that scientists are losing their ability to pages 76–81; March 7, 2002. recognize early life, though, remember Metasomatic Origin of Quartz-Pyroxene Rock, Akilia, Greenland, and Implications for Earth’s Minden Pictures that the brouhaha over Akilia and Apex Earliest Life. Christopher M. Fedo and Martin J. Whitehouse in Science, Vol. 296, pages 1448–1452; May 24, 2002. are just about being the very oldest signs Magnetofossils from Ancient Mars: A Robust Biosignature in the Martian Meteorite ALH84001. of life. That’s important but not the be-all Kathie L. Thomas-Keprta et al. in Applied and Environmental Microbiology, Vol. 68, No. 8,

MITSUAKI IWAGO and end-all. Rocks at Isua and South pages 3663–3672; August 2002.

www.sciam.com SCIENTIFIC AMERICAN 77 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. By linking digital processors, storage systems and software on a global scale, grid technology is poised to transform computing from an individual and corporate activity into a general utility

THE GRID: Computing without Bounds By Ian Foster

COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. Early humans ate only the food they caught and used only the tools they made. Millennia of effort to overcome the cou- computer and even a sophisticated cor- to changes in demand while simultane- pling of production and consumption porate data center are largely self-con- ously linking those systems to partners, eventually led to agriculture, mass manu- tained systems running locally stored soft- suppliers and customers to expand the facturing and electric power distribution. ware programs. We would not accept a services they receive. Imagine an adven- The resulting specialization of work, situation in which every home and busi- ture travel firm that provides virtual-re- economies of scale and novel technologies ness had to operate its own power plant, ality explorations of its dive locations. As define our modern world—and allow me library, printing press and water reservoir. a potential customer starts to navigate the to sit in a café sipping an espresso and Why should we do so for computers? virtual waters off Cozumel, the company writing this article on a laptop computer, This less-than-optimal state of affairs needs to access databases and software to with no thought to the ultimate sources of has motivated computer scientists to retrieve relevant geographic information, the water, coffee, electricity and wireless- look for more efficient alternatives. Dig- render data into three-dimensional graph- network bandwidth that I consume. ital networks are getting faster and faster, ics, superimpose the appropriate com- The ready availability of these re- so why not assemble “computers” dy- mercial information and integrate real-

sources exempliﬁes the concept of virtu- namically from distributed pieces so that time video from on-site cameras. No ) alization, which (to computer scientists) users can call on resources—processing, travel company could afford to operate below refers to hiding useful functions behind storage, data and software—regardless of these capabilities itself. But with grid an interface that conceals the details of location and from any suitable supplier? technologies, the necessary resources can how they are implemented. When the That is, why not virtualize general com- be assembled from multiple suppliers, café’s barista, for example, turns on a putational services? Such a computing each serving many clients and thus water spigot, it is as if he taps a bottom- “grid” could be as ubiquitous as the elec- achieving favorable economies of scale ); GEORGE RETSECK ( less barrel. The same phenomenon oc- tric grid—and just as useful. [see box below]. curs when I plug my laptop into a wall Grid systems hold promise for more socket. Given the huge unseen electric Grid Business esoteric domains as well. In medicine, ac-

grid beyond the plug, who knows how LIKELY BENEFICIARIES of a pervasive cess to remote computers and databases preceding pages and where that power was generated? computing grid would include e-com- could allow my physician to compare my Computing itself, however, is any- merce enterprises, which could tailor x-rays with those of a million other pa-

thing but virtualized. My laptop, a home their information and computing systems tients, perhaps enabling him to catch a SLIM FILMS ( GRID-ENABLED VIRTUAL-REALITY DIVE TOUR

TO VISUALIZE what a full-ﬂedged grid-computing system could do in the The small company can manage to deliver this supercomputerlike commercial arena, imagine an adventure travel firm (ScubaTours) that capability by employing the grid to contract out the task of assembling provides virtual-reality explorations of its diving locations. This service the far-flung computational resources needed to produce a realistic allows a potential customer armed only with a home computer and simulation. When a potential customer wants to navigate the virtual joystick to “ﬂy through” a detailed three-dimensional representation of Caribbean waters, ScubaTours’s computers contact remote servers that a coral reef—in this case, one lying off the Mexican resort of Cozumel. handle the details of accessing remote databases and software. These

HOME COMPUTERS COMPUTERS, INC.’S COMPUTERS, INC. COMPETITORS

ONLINE GAME FIRMS COMPUTER GAMES CORP. VIRTUAL DIVE GRAPHICS DATA CUSTOMER

CREDIT CARD COMPANY SCUBATOURS

80 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. Overview/Grid Computing malignancy earlier. Elsewhere it might let biochemists screen 10,000 drug candi- ■ Grid computing refers to the large-scale integration of computer systems dates in an hour rather than in a year or (via high-speed networks) to provide on-demand access to data-crunching allow civil engineers to test an earth- capabilities and functions not available to one individual or group of machines. quake-resistant bridge design in minutes ■ Using shared languages and interaction protocols, grid systems reach out rather than months. across the globe to access the computing resources, information and services This concept of globally virtualized required to satisfy local user needs. grid computing is a natural extension of ■ To users, the highly integrated networks that embody grid systems are today’s Internet. The Internet virtualizes transparent—it seems as if the services furnished from afar are provided communications, permitting any person by local computers. or device to connect with any other per- ■ Grid technology enables large-scale scientific and business collaboration son or device, regardless of location or the among members of virtual organizations, remote experimentation, and means used to do so. The result has been high-performance distributed computing and data analysis. an explosion of innovative functions: e- mail, the World Wide Web, peer-to-peer through a fascination with how compu- to search for interesting correlations. applications, including file-sharing sys- tational tools can enhance human intel- Thus, in 1994 I decided to refocus my tems such as KaZaA, and simple distrib- lect. In the early 1990s I was working on research on distributed computing. With uted-computing schemes such as SETI tools for scientific computing at the U.S. partners Steven Tuecke of Argonne and @home, FightAIDS@home and the Small- Department of Energy’s Argonne Na- Carl Kesselman, then a research fellow at pox Research Grid. The goal of those of tional Laboratory. High-speed networks the California Institute of Technology us now developing the grid is to virtualize were starting to appear, and it became and now director of the Center for Grid computing and information so that any clear that if we could integrate digital re- Technologies at the University of South- person or device can furnish software ser- sources and activities across networks, it ern California’s Information Sciences In- vices to any other and—equally signifi- could transform the process of scientific stitute, I established a project to create a cant—so that access to disparate collec- work. Lab instruments, for instance, could software system that would enable sci- tions of such services will be secure and be linked with remote computers to en- entific collaboration on a worldwide reliable. able real-time data analysis. And multiple scale. We gave this effort the somewhat My interest in grid computing arose distributed databases could be combined grandiose name the “Globus Project.”

servers thus retrieve relevant cartographic and image information, and brokers (such as Computer Games Corp., and Computers, Inc.), render data into three-dimensional graphics, integrate real-time each serving many clients and thus achieving favorable economies of video from on-site cameras, and superimpose appropriate scale. Other providers on the grid (not shown) offer reputation commercial information. All these assets, as well as the software that management, billing, and similar functions. [See page 85 for a more generates a compelling virtual experience, are obtained via a mix of detailed explanation of how grid systems could enable this long-term contracts and competitive bidding from multiple suppliers sophisticated business application.]

COMPUTATIONAL-CYCLE PROVIDERS SUBMERGED REEF VIDEO CAMERAS

LIVE VIDEO FEED COZUMEL CAMERAS

COZUMEL TOURIST BOARD AIRLINES COZUMEL HOTELS

www.sciam.com SCIENTIFIC AMERICAN 81 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. SELECT INTERNATIONAL GRID PROJECTS NAME WEB ADDRESS SPONSORING INSTITUTIONS FOCUS Biomedical Informatics www.nbirn.net U.S. National Institutes Integration and analysis of biomedical data Research Network of Health Department of Energy doesciencegrid.org U.S. DOE Office of Science Links resources and applications at DOE Science Grid science laboratories Earth System Grid www.earthsystemgrid.org U.S. DOE Office of Science Analysis of large climate-model data sets European Grid of www.mssl.ucl.ac.uk/grid/egso European Union Integration of research by European Solar Observatories solar-data centers European Union DataGrid www.eu-datagrid.org European Union Applications in high-energy physics, environmental science and bioinformatics GridLab gridlab.org European Union Grid technologies and applications Grid Physics Network griphyn.org U.S. National Data analysis for large-scale physics Science Foundation experiments Information Power Grid www.ipg.nasa.gov NASA (U.S.) Aerospace sciences research support MyGrid www.mygrid.org.uk U.K. e-Science program Workbench for bioinformatics applications National Fusion Grid www.fusiongrid.org U.S. DOE Office of Science Computational fusion research National Research Grid Initiative www.naregi.org Japanese Ministry of Education Japanese national research grid project National Virtual www.us-vo.org U.S. National Science Integration and analysis of Observatory Foundation astronomical data Network for Earthquake www.neesgrid.org U.S. National Science Earthquake engineering research Engineering Simulation Foundation Particle Physics Data Grid ppdg.net U.S. DOE Office of Science Data analysis in high-energy and nuclear physics experiments Singapore BioGrid www.bic.nus.edu.sg/biogrid Singapore government Bioinformatics TeraGrid teragrid.org U.S. National Science High-speed infrastructure links among Foundation four major science-resource sites WorldGrid ivdgl.org/demo/worldgrid U.S. DOE, National Science International infrastructure for Foundation, European Union data-intensive science

Distributed computing is by no means communities require technologies that al- rather by linking them into a VO struc- a new idea: many concepts that underlie low groups of collaborators located at ture. The software would accomplish this today’s grid systems predate even the In- different institutions—what we called task by standardizing a variety of func- ternet. Back in the mid-1960s, for exam- virtual organizations (VOs)—to share re- tions—most important, the ability to au- ple, Fernando Corbato, the father of sources in a controlled and well-managed thenticate identity, to authorize a re- time-sharing operating systems, de- manner. Rather like professional soccer quested activity, to define and access scribed the then revolutionary Multics players pulled from separate clubs to available resources, and to control the system as a “computing utility.” The train together as a national team to com- movement of data. Because these VO banking and airline industries have run pete in the World Cup, such scientific utilities would operate on top of existing sophisticated distributed systems for VOs cut across conventional institution- computational structures, they could decades. We, however, approached the al boundaries, creating, of course, myri- achieve these goals at an acceptable cost. problem from a different perspective, one ad organizational and policy problems. defined by the needs of scientific research VO participants in particular need to Early Grid Work communities. In our experience, the of- share information, computers, storage OUR IDEAS WERE PUT to the test ten extreme requirements and only par- and software in a controlled fashion as sooner than we anticipated. In late 1994 tially controlled chaos of scientific inves- they engage in collaborative work, but Rick L. Stevens, director of the mathe- tigation can be strong drivers for inno- unlike the soccer players, they might not matics and computer science division at vation. It seems no coincidence that the wear the same uniforms, speak the same Argonne, and Thomas A. DeFanti, di- World Wide Web was invented by Tim language, follow the same rules, or per- rector of the Electronic Visualization Berners-Lee, a computer scientist whose haps even play the same game! Laboratory at the University of Illinois at work with high-energy physicists in- Kesselman, Tuecke and I envisioned Chicago, proposed establishing tempo- spired him to create a universal system a new class of integrating software that rary links among 11 high-speed research for sharing information. would enable this sharing, not by replac- computer networks to create a national In our case, we saw that scientific ing systems at participating sites but grid (the “I-WAY”) for the two weeks

82 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. before and during an industry conference makes nearly seamless interoperability lion celestial objects. By harnessing com- called Supercomputing ’95. Their call for important to any resource-sharing infra- putational resources at labs across the na- applications for the system generated structure. It has helped that almost all ef- tion, we aim to allow scientists to perform more than 60 responses from scientists. forts to develop grid systems build on the what are now weeklong scans in the time Stevens and DeFanti also persuaded Globus Toolkit, but it was clear that well- it takes to brew a cup of coffee. me and a small team of co-workers at Ar- defined, community-based technical stan- This group has already generated a gonne to develop the software that knit- dards would be essential if grid computing database of galaxy clusters, which inter- ted the 17 participating I-WAY sites into were to expand beyond its initial users. ests cosmologists working on theories de- a single virtual system. These protocols al- Therefore, in 1998 several of us convened scribing the birth of the universe. Next is lowed users to run applications on com- the first meeting of what two years later a search for near-Earth objects, a topic puters across the country. Users could log became the Global Grid Forum, an inter- that concerns us all, given that asteroids on once, locate suitable computers, re- national user-community and standards will one day strike our planet. This effort serve time, load application codes, and organization. feeds into a far more ambitious interna- then monitor their execution. In one ex- tional undertaking focused on linking ample, a group led by Lori Freitag of Ar- Exploiting the Grid many such astronomical databases into a gonne constructed a network that al- GRID TECHNOLOGIES are infrastruc- global virtual observatory. lowed combustion engineers across the ture, which doesn’t make for compelling Grid technologies are also making U.S. to work collaboratively on improve- reading—after all, when infrastructure their mark in clinical medicine, where dig- ments to industrial incinerators. works, it is as invisible as the sewage sys- ital imaging has made it easier to compare The I-WAY experiment was a great tem. The grid infrastructure has made mammograms and other body scans both success and inspired much that followed. possible some virtualized projects that across time for individual patients and The U.S. Defense Advanced Research are compelling, however. across case populations. But the im- Projects Agency gave the Globus Project Ever since Galileo pointed his tele- proved scanning systems mean contend- money for more research. In 1997 we un- scope at Saturn, long, cold nights in the ing with a deluge of visual data. Current- veiled the first version of our grid soft- observatory have been the astronomer’s ly experts estimate that one fifth of first- ware system, the Globus Toolkit, and lot. Yet advances in computing and sen- time mammograms are misdiagnosed. demonstrated its operation across 80 sor technologies are now enabling a new Further, in 20 percent of all cases, previ- sites worldwide. Meanwhile the Nation- generation of “armchair astronomers” to ously prepared images cannot be located. al Science Foundation funded the cre- make significant advances. Rather than Digital image libraries now being creat- ation of the National Technology Grid to freezing in nighttime isolation, these as- ed by projects such as the National Digi- connect university scientists with high- tronomers sit in comfortable offices dur- tal Mammography Archive in the U.S. end computers, NASA started work on its ing the day, instructing computers to and eDiamond in the U.K. are addressing Information Power Grid (which had sim- mine digital sky surveys. For these New these problems. These grid systems also ilar goals), and the DOE initiated pio- Age astronomers, a principal obstacle to link physicians with advanced analytical neering work on applying grids to science progress is not a shortage of telescope tools for automated diagnosis and permit research. time but the difficulty in finding the soft- researchers to conduct in-depth studies to The remainder of the 1990s saw ware, storage, network and computing determine the effects of environment and growing implementation of grid concepts resources they need to analyze the vast lifestyle choices on disease [see box on and technology. The high-energy physi- amounts of data these surveys produce. next page]. cists designing the Large Hadron Collid- A team at the University of Chicago, Another health-related imaging grid, er at CERN, the European organization Fermilab and the University of Wiscon- the U.S. Biomedical Informatics Research for nuclear research, for instance, recog- sin–Madison has been looking for ways Network, is integrating body-scan data nized that a grid system would be essen- to apply grid technologies to the analy- from various sources to allow compara- tial to their analysis of the huge quantities sis of data from one of these new archives, tive studies of brain images from many of data the new accelerator was to pro- the Sloan Digital Sky Survey. This exten- databases. This grid may help answer duce. Projects were subsequently estab- sive effort to map a quarter of the night questions such as “How are brain struc- lished to develop the needed grid tech- sky will determine the positions and ab- tures in Alzheimer’s patients different nologies, notably the European Data- solute brightnesses of more than 100 mil- from those organs in healthy people?” Grid, as well as the U.S. Grid Physics Network and Particle Physics Data Grid IAN FOSTER is originally from New Zealand. He now resides in Chicago, where he is associ- efforts. These and similar undertakings ate director in the mathematics and computer science division at Argonne National Labo- spurred the development of grid-related ratory and professor of computer science at the University of Chicago. Foster also serves infrastructure, user communities and new on the advisory boards of several companies, including Entropia and Insors. His many hon- software applications. ors include the Global Information Infrastructure Next Generation award and the British The international nature of science THE AUTHOR Computer Society’s Lovelace Medal.

BY ENABLING ACCESS to all kinds of computational resources being implemented for the National Digital Mammography from afar, grid computing is transforming the way enormous Archive is creating a vast virtual ﬁle cabinet that can not only processing tasks are accomplished. Digital mammography is a reliably store and transfer these images with little loss of detail case in point. Computer-based breast imagery yields more but can make possible real-time expert consultation and the use accurate diagnoses than do ﬁlm-based photographs. But storing of computer-aided diagnosis techniques from across the and accessing the estimated 28 terabytes of image country. Thus, a patient’s mammogram can be readily data that can be generated every day in the U.S. is a compared both with her previous images and with those huge problem. Grid-computing technology of similar patient groups. COMPUTER-AIDED DIAGNOSIS SYSTEM

EXPERT ANALYSIS PHYSICIAN/PATIENT CONSULTATION

The U.S. Network for Earthquake En- Platform, Sun and United Devices. Phras- Equivalent success in the computing gineering Simulation (NEES) shows how es such as “utility computing,” “e-business industry could lead to a computational grid technologies can support experimen- on demand,” “planetary computing,” ecosystem made up of manufacturers, dis- tation. Civil engineers designing earth- “autonomic computing,” and “enterprise tributors and consumers. Producers could quake-resistant structures test their con- grids” have become increasingly common gain economies of scale and improve se- cepts in experimental facilities housing in marketing literature and business plans. curity and reliability. Distributors could equipment such as shake tables and cen- To understand this growing interest, focus on brokering consumer demand trifuges. Part of the $82-million program we must look at the high costs and endless with available resources and on finding focuses on assembling a NEESgrid that frustration associated with operating com- novel forms of value-added services. Con- links existing and newly constructed test puters, an endeavor that has never pro- sumers could avail themselves of a rapid- facilities with data archives, computa- gressed much beyond what is essentially ly developing array of applications and tional resources and the nationwide com- still a cottage industry. We all know that devices powered by new remote services. munity of users. NEESgrid makes it pos- users spend far too much time installing, Many innovative technologies are re- sible for researchers at remote sites to maintaining, troubleshooting, fixing and quired to make this vision of grid-enabled participate in experiments taking place upgrading their private systems, which computing a reality. The Internet and the elsewhere. Planned for this summer, for furthermore do not work well together. World Wide Web allow us to send mes- example, is a study of bridge columns that Grid computing offers the promise of sages and access Web pages from just will be tested simultaneously on shake ta- overcoming these problems by decoupling about anywhere, but much more is re- bles in California and Illinois. Networks production and consumption, thereby en- quired if users are to share resources on will communicate the relevant force-feed- abling specialized functions and common a large scale. In effect, we have speech but back levels, generating data about how services to be turned into commodities. not yet a common language. Collabora- structures behave in earthquakes. Progress toward this goal will be any- tors need to agree on how services are de- thing but straightforward. Similar tran- scribed, how parties establish one anoth- Laying Down the Grid sitions, however, have occurred in fields er’s identity, how access rules are de- SCIENTISTS ARE NOT the only ones such as manufacturing, electric power scribed and verified, and how activities who are excited by the potential of grid and telephony. The automobile, for ex- are conducted. computing. Since 2000, more and more ample, was initially a luxury plaything of The grid community took a signifi- companies have pursued commercial ap- expert hobbyists. Today cars and trucks cant step toward addressing these issues plications for grid technologies, includ- are driven by nearly everyone in the de- with the launch in 2002 of an initiative to ing Avaki, DataSynapse, Entropia, Fujit- veloped world, with support from a vast define the Open Grid Services Architec-

su, Hewlett-Packard, IBM, NEC, Oracle, global production and service network. ture. This system architecture integrates GEORGE RETSECK

84 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. Web services technologies that have be- Once the engineers have negotiated nologies. Hence, it is important that not come popular in industry with the grid access to equipment at Computers, Inc., only all key grid specifications be freely techniques pioneered by the scientific Computer Games Corp. must load its available to everyone but that an open, community. software and manage the virtual dive ex- easy way to implement those specifica- perience. Perhaps the customer will head tions exists. The Globus Toolkit fills this Plugged into the Grid in an unexpected direction, increasing requirement. Further progress depends TO ILLUSTRATE what a full-fledged computational requirements, or perhaps on contributions from academia and in- open architecture can do, let’s return to some computers or networks will fail. In dustry and from commercial support our adventure travel company, Scuba- either case, Computer Games Corp. has vendors, as well as on integration of grid Tours [see box on page 80]. What hap- to incorporate additional computers or concepts into commercial software and pens when a customer asks for a virtual reduce the fidelity of the simulation. third-party training. dive off Cozumel? ScubaTours first es- Notice that these interactions require tablishes that the customer has a broad- standard languages for describing, adver- Where Next? band connection, determines what the tising and querying the capabilities sup- HAVING ATTAINED success within the customer wants to see, and then hands plied by resource operators and for mak- relatively friendly confines of scientific responsibility for fulfilling the request to ing conversations among the participants collaborations and corporate intranets, a specialized virtual-reality service pro- possible. Mechanisms for establishing grid technologies are expanding to larg- vider, Computer Games Corp. (Computer identity, accounting for usage, organizing er communities, including those based on Games Corp. also supports multipartici- payment, and so on are also needed. Soft- purely commercial relationships. Stan- pant Internet gaming companies, hence ware for accomplishing many of these dardization is spurring investment and its name.) Computer Games Corp. in turn tasks is included today in the Globus innovation. During the next few years, assembles the data and software required Toolkit, and more general standards are this work will establish the basis for a to deliver the desired “fly-through”— being disseminated by Global Grid Fo- global grid system. streaming video generated in response to rum working groups. Meanwhile grid researchers are tack- the user’s navigational commands. Its I expect standardization to spur in- ling the next set of challenges: How can computers reach out into the grid to lo- novation and competition in computing we manage large, distributed infrastruc- cate the most attractive supplier of com- services, just as it has in other industries. tures so that they deliver reliable service putational cycles for the rendering of the It could become feasible to use aggregat- in the face of failures? How can we enable video stream. Computer Games Corp. ed desktop or even home computers as a users to exploit the availability of on-de- then installs this software, and the virtu- significant computing and storage re- mand resources and services? How must al dive gets under way. In effect, Comput- source. We find, for instance, that about grid concepts and technologies evolve as er Games Corp. acts as a middleman, ag- half the computing resources employed the number and power of computers rise gregating services from several sources to in the Sloan Digital Sky Survey were from by orders of magnitude? The answers will afford a specialized capability to the user. desktop systems aggregated by a system emerge from both research and practical Although these negotiations should called Condor. Companies such as Data- experience and will surely draw on ideas appear transparent to the customer, mak- Synapse, Entropia, Platform and United being pioneered in the related fields of au- ing them work is far from easy. Comput- Devices are implementing grid protocol tonomic, ubiquitous and peer-to-peer er Games Corp. engineers must have al- interfaces to desktop computer pools to computing [see “The Worldwide Com- ready built specialized software able to enable virtualized computing. puter,” by John Kubiatowicz and David run on multiple computers, and they The success of grid computing de- P. Anderson; Scientific American, must know how to estimate and then lo- pends on its broad adoption. One proven March 2002]. These disciplines are all cate the computing power and network strategy for overcoming this classic catch- converging on the same vision of the com- capacity they need. To this end, they con- 22 is to provide free access to core tech- puting environment of tomorrow. tact a trusted “broker” who serves as a clearinghouse for computing services. MORE TO EXPLORE Having located a suitable candidate, say, The Grid: Blueprint for a New Computing Infrastructure. Edited by I. Foster and C. Kesselman. Computers, Inc., they can contact it di- Morgan Kaufman, 1999. (Second edition in press.) rectly using some common language. The Grid: A New Infrastructure for 21st Century Science. I. Foster in Physics Today, Vol. 55, Then they negotiate to establish mutual- No. 2, pages 42–47; 2001. ly acceptable bona fides (“I am not a The World-Wide Telescope. A. Szalay and J. Gray in Science, Vol. 293, pages 2037–2040; 2001. hacker” and “I am able to pay” and “You The Physiology of the Grid: An Open Grid Services Architecture for Distributed Systems Integration, 2002. I. Foster, C. Kesselman, J. Nick and S. Tuecke. are an established company”) and to de- www.globus.org/research/papers/ogsa.pdf termine the terms of the transaction (the Grid Computing: Making the Global Infrastructure a Reality. Edited by F. Berman, G. Fox and number of computers, performance, cost T. Hey. John Wiley & Sons, 2003. and so forth). More information can be found at www.mcs.anl.gov/~foster

www.sciam.com SCIENTIFIC AMERICAN 85 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. FAN-SHAPED LEAVES of the ginkgo tree are shown in this drawing from Flora Japonica, a book written by 19th-century German physician Philipp Franz von Siebold. The extract obtained from the leaves (inset on opposite page) is one of the most widely used herbal treatments aimed at improving memory.

86 SCIENTIFIC AMERICAN COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. THE LOWDOWN ON GINKGO BILOBA This popular herbal supplement may slightly improve your memory, but you can get the same effect by eating a candy bar

By Paul E. Gold, Larry Cahill and Gary L. Wenk

he ginkgo tree (Ginkgo biloba) is remarkable )

above in many ways. Although indigenousT to Korea, China and Japan, the tree can be found in parks and along city sidewalks around the world. It may grow as high as 40 meters and live for more than 1,000 years. Ginkgo fossils have been dated as

); GETTY IMAGES ( far back as 250 million years ago, and Charles Darwin referred to test the effectiveness or safety of their products. More atten- to the tree as “a living fossil.” Nowadays, however, the ginkgo’s tion to supplements such as ginkgo biloba is clearly warranted; primary claim to fame is the extract obtained from its fan- even if the products do not cause medical problems, they can

opposite page shaped leaves. be costly and may prevent patients from seeking more pragmatic The use of ginkgo leaf extracts can be traced back for cen- treatments. In an attempt to close the gap in our knowledge, we turies in traditional Chinese medicine. Today ginkgo biloba is have reviewed the experimental evidence both for and against perhaps the most widely used herbal treatment aimed at aug- the usefulness of ginkgo biloba in enhancing brain functions. menting cognitive functions—that is, improving memory, learning, alertness, mood and so on. Ginkgo is especially popular in Many Studies, Few Answers Europe; officials in Germany recently approved the extract for THE TYPICAL DAILY DOSE of ginkgo biloba—and the one treating dementia. In the U.S. the National Institute on Aging is used in many of the experiments described in this article—is 120 currently supporting a clinical trial to evaluate the efficacy of milligrams of dried extract in two or three oral doses. The ex- BY SIEBOLD AND ZUCCARINI, LEIDEN 1835/42, IN THE UNIVERSITY ginkgo in treating the symptoms of Alzheimer’s disease. tract contains several flavonoids, a large group of natural plant But is there any evidence that ginkgo biloba can really im- products that are characterized by a specific chemical structure prove cognitive functions? Information on most dietary supple- containing a series of carbon rings. Ginkgo extract also contains ments is based far more on folklore than on experimental find- some biflavonoids, a related group of compounds, and two dif- FLORA JAPONICA, ings. Because the U.S. Food and Drug Administration does not ferent types of terpenes, a class of naturally occurring chemicals FROM BRANCH OF THE NATIONAL HERBARIUM NETHERLANDS ( regulate herbal treatments, the manufacturers are not required that includes the active ingredients in catnip and marijuana.

www.sciam.com SCIENTIFIC AMERICAN 87 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. Ginkgo’s Effects on the Brain RESEARCHERS CANNOT SAY FOR CERTAIN WHETHER GINKGO BILOBA CAN IMPROVE COGNITIVE FUNCTIONS, BUT THEY HAVE FOUND THAT THE EXTRACT CAN AFFECT THE BRAIN IN SEVERAL WAYS

CIRCULATORY BRAIN REGIONS AFFECTED Cerebral arteries ■ Stimulates widening of the blood vessels, which leads to increased blood flow to the brain and lowered blood pressure (perhaps reducing the risk of stroke). ■ Reduces cholesterol levels in the blood (excessive cholesterol is Frontal cortex Parietal correlated with an increased risk of Alzheimer’s disease). cortex ■ Inhibits the aggregation of blood platelets and the formation of clots. This may lower the risk of an occlusive stroke (caused by a Nucleus clot blocking a blood vessel in the brain) but raise the chance of a Occipital accumbens cortex hemorrhagic stroke (caused by bleeding in the brain). Hippocampus ANTIOXIDANT Cerebellum ■ Curbs the creation of free radicals, highly reactive oxygen molecules that may injure neurons and cause age-related changes in the brain. ■ Alleviates the effects of cerebral ischemia—the loss of blood flow to the brain—by inhibiting the production of toxic free radicals from the blood. Choline is one of the components of acetylcholine, after an ischemic episode. a brain chemical that transmits signals between certain neurons. ■ Slows the attrition of neuron receptors that direct the response to GLUCOSE UTILIZATION serotonin, a neurotransmitter that reduces stress and anxiety. ■ Boosts the absorption of glucose, the body’s primary fuel, in the ■ Enhances the release of gamma-amino butyric acid (GABA), frontal and parietal cortex, areas of the brain important for another neurotransmitter that can relieve anxiety. Lowering processing sensory information and for planning complex actions. stress may reduce the level of glucocorticoid hormones in the ■ Also increases glucose absorption in the nucleus accumbens and blood, which in turn may protect the hippocampus, a brain the cerebellum, brain regions involved in experiencing pleasure structure critical to normal learning. and controlling movement, respectively. ■ Raises the production of norepinephrine, yet another neurotransmitter. Enhanced activation of the norepinephrine NEUROTRANSMITTER SYSTEMS system by certain antidepressants has been shown to reduce the ■ Appears to help neurons in the forebrain absorb the nutrient choline symptoms of depression.

To date, dozens of investigations have examined the cogni- Because the studies have varied so greatly in the numbers of tive effects of ginkgo in humans, but many of the research re- subjects and the control over experimental conditions, it is use- ports are in non-English publications or in journals with very re- ful to focus on only the most rigorous investigations. In 1998 stricted distribution, making assessment of the findings difficult. Barry S. Oken of Oregon Health Sciences University and his col- The great majority of studies have involved subjects with mild leagues considered more than 50 studies involving subjects with to moderate mental impairment, usually a diagnosis of early Alz- mental impairment and selected four that met a conservative set heimer’s. Most of the experiments that show evidence of cog- of criteria, including sufficient characterization of the Alzheim- nitive enhancement in Alzheimer’s patients have used a stan- er’s diagnosis, use of a standardized ginkgo extract, and a place- dardized ginkgo extract known as EGb 761. bo-controlled, double-blind design (in which neither the subjects The ginkgo researchers have usually employed tests of learn- nor the investigators know until the end whether a given patient ing and memory; less attention has been paid to other mental is receiving the extract or the placebo). Each of these studies functions such as attention, motivation and anxiety. Moreover, showed that the Alzheimer’s patients who received ginkgo per- because most of the investigators introduced the tests to the sub- formed better on various cognitive tests than did patients who jects after long-term use of ginkgo biloba (typically several received a placebo. Improvements were evident in standardized months), it is hard to identify which cognitive abilities have been tests measuring attention, short-term memory and reaction time; affected. For example, higher scores on the memory and learn- the average extent of improvement resulting from ginkgo treating tests might stem from the fact that subjects who used gink- ment was 10 to 20 percent. go paid better attention to the initial instructions. To get more Oken and his colleagues reported that ginkgo’s effect was specific data on ginkgo’s effects, researchers need to administer comparable to that of the drug donepezil, which is currently the

the tests both before and after the subjects take the supplement. treatment of choice for Alzheimer’s. Donepezil enhances brain ALICE Y. CHEN

88 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. activity by inhibiting the breakdown of acetylcholine, a brain University of Leeds in England administered a battery of tests chemical that transmits signals between certain neurons. Despite to eight healthy subjects (ages 25 to 40) after they took the gink- these apparently encouraging ﬁndings, though, another recent, go extract EGb 761. Hindmarch reported that the highest dose large and well-controlled trial of EGb 761 (sponsored by its tested (600 milligrams) improved performance in only a short- manufacturer, Dr. Willmar Schwabe Pharmaceuticals in Karls- term memory test. More recently, two reports from Cognitive ruhe, Germany) involving patients with a mild or moderate stage Drug Research, a laboratory in Reading, England, provide mi- of dementia reported no “systematic and clinically meaningful nor support for the view that ginkgo may enhance cognitive effect of ginkgo” on any of the cognitive tests employed. functions in young people. One study reported that subjects A critical question concerns whether the ginkgo treatment who took a dose of ginkgo performed better on tasks assess- in studies showing positive effects actually improved cognitive ing attention than did subjects who took a placebo. The other abilities in Alzheimer’s patients or merely slowed their deteri- study showed an improvement in memory among middle-aged oration. Two different answers to this key question have come subjects (ages 38 to 66) who were treated with a combination from a 1997 investigation led by Pierre L. Le Bars of the New of ginkgo and ginseng, another herbal remedy touted as a mem- York Institute for Medical Research. In this study, which was ory aid. The effects seen in the latter study, however, could not Information on most dietary supplements is based far more on folklore than on EXPERIMENTAL FINDINGS.

one of the four analyzed by Oken, the results varied according be attributed to ginkgo alone and did not increase with the to the cognitive test that was employed. Measured by the Alz- dosage, which would be expected of a truly effective substance. heimer’s Disease Assessment Scale Cognitive Subscale, the per- For most pharmaceuticals, researchers conduct a large num- formance of the patients treated with the placebo slowly dete- ber of studies with lab animals before they test the drugs in hu- riorated over a year, whereas the performance of patients treat- mans. Such experiments can be useful in determining a drug’s ed with ginkgo remained stable. But according to a second safety and effectiveness. But because ginkgo is unregulated, its test—the Geriatric Evaluation by Relative’s Rating Instru- manufacturers have not been required to perform animal tests. ment—ginkgo-treated subjects improved by about the same As a result, there are relatively few research reports in refereed amount that placebo-treated subjects deteriorated. journals examining the efficacy of ginkgo in improving learning Furthermore, at least one study has reported positive effects and memory in animals. Perhaps the most notable example is a on mentally impaired subjects after just a single treatment of 1991 study of young adult mice that were trained to press a lever ginkgo. Herve Allain of the University of Haute Bretagne in to receive food. Mice treated with ginkgo for four to eight weeks Rennes, France, gave one fairly high dose of ginkgo—320 or 600 learned the task slightly more quickly than did the control mice. milligrams—to a small group of elderly people with mild, age- As with humans, though, it is difficult to pin down whether gink- related memory impairment. An hour after the treatment, Al- go actually enhances the learning process or whether it has oth- lain tested the subjects’ memory by rapidly presenting short lists er effects that improve the animals’ performance at a specific of words or drawings and then asking the patients to recall the task. For instance, investigators have reported that repeated ad- lists immediately afterward. Their ability to recall the rapidly ministration of ginkgo reduced stress in rats, and altered stress presented material increased significantly after ingestion of gink- responses can themselves have a great influence on learning and go. This finding raises the possibility that short-term, rather than memory. long-term, biological actions provide the basis for ginkgo’s re- If ginkgo can really enhance mental processes, how does it ported effects on cognition. work? Studies of humans and lab animals have indicated sever- It should be noted that ginkgo has also been shown to im- al classes of biological effects that might contribute to ginkgo’s pair performance. For example, in a small study of elderly peo- putative improvement of cognitive functions [see box on oppo- ple with mild to moderate memory impairment, Gurcharan S. site page]. Whatever its effects, ginkgo appears to pose few health Rai of Whittington Hospital in London and his team found that after 24 weeks of treatment, patients who took ginkgo could PAUL E. GOLD, LARRY CAHILL and GARY L. WENK are leading au- not recall digits as well as patients who received a placebo. thorities on the enhancement of brain functions. Gold is professor FoodPix of psychology and neuroscience at the University of Illinois at Ur- Help for the Healthy? bana-Champaign. Cahill is assistant professor of neurobiology and UNFORTUNATELY, FAR FEWER studies have examined the behavior and fellow of the Center for the Neurobiology of Learning cognitive effects of ginkgo biloba on healthy young adults. In and Memory at the University of California, Irvine. Wenk is profes- THE AUTHORS

MONICA STEVENSON one small study during the mid-1980s, Ian Hindmarch of the sor of psychology and neurology at the University of Arizona.

www.sciam.com SCIENTIFIC AMERICAN 89 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. The Other “Brain Boosters” ACETYL-L-CARNITINE (ALC) By Mark A. McDaniel, Steven F. Maier and Gilles O. Einstein An amino acid included in some “brain power” supplements sold in health food stores, ALC participates in cellular energy production, a OLDER ADULTS HAVE shown a strong interest in over-the-counter process especially important to neurons. Animal studies show that “brain boosters,” many of which are marketed with grand claims ALC reverses age-related decline in the number of receptor touting their benefits. There are sound biochemical reasons for molecules on neuronal membranes. But studies of patients with expecting some of these nutrients to be effective. In a review of probable Alzheimer’s have reported only nominal advantages for published research, we found studies showing that some of these ALC in a range of memory tests. substances had robustly enhanced memory in lab animals and occasionally produced impressive improvements in humans as ANTIOXIDANTS well. Nevertheless, there are numerous questions about the Antioxidants such as vitamins E and C help to neutralize tissue- sample sizes in the studies, the generality of the results across damaging free radicals, which become more prevalent with age. different memory tests and populations, and other aspects of the But studies have found that vitamin E does not offer significant procedures and data. These problems, in conjunction with a general memory benefits for patients with Alzheimer’s or early Parkinson’s lack of research demonstrating that the results can be replicated, disease. A combination of vitamins E and C did not improve college dampen enthusiasm for the effectiveness of these nutrients in students’ performance on several cognitive tasks. substantially arresting or reversing memory loss. Here is an abbreviated summary of the findings for six kinds of A more detailed version of this article appeared as “Brain-Specific nonprescription compounds that are claimed to be memory Nutrients: A Memory Cure?” by Mark A. McDaniel, Steven F. Maier and enhancers and treatments for age-related memory decline. Gilles O. Einstein in Psychological Science in the Public Interest (May 2002). (Available at www.psychologicalscience.org/journals/ PHOSPHATIDYLSERINE (PS) pspi/3–1.html) McDaniel is chair of the department of psychology at A naturally occurring lipid, PS has been shown to reduce many the University of New Mexico. Maier is director of the Center for consequences of aging on the neurons in older rats and mice and to Neuroscience at the University of Colorado at Boulder. Einstein is restore their normal memory in a variety of tasks. Research on the chair of the department of psychology at Furman University. impact in humans is limited, though. For older adults with moderate cognitive impairment, PS has produced modest increases in recall of word lists. Positive effects have not been as consistently reported for other memory tests.

CHOLINE COMPOUNDS Phosphatidylcholine, which is typically administered as lecithin, has not proved effective for improving memory in patients with probable Alzheimer’s disease. Research on citicoline is practically nonexistent, but one study reported a robust improvement in story recall for a small sample of normally aging older adults.

PIRACETAM Developed in 1967, Piracetam has not been approved by the U.S. Food and Drug Administration, but it is sold in Europe and Mexico under several names (including Nootropil and Pirroxil). Animal studies suggest that the drug may improve neural transmission and synaptic activity and also combat age-related deterioration of neuronal membranes. But there is no clear sign of any cognitive benefits in patients with probable Alzheimer’s or adults with age- associated memory impairment.

VINPOCETINE An alkaloid derived from the periwinkle plant, vinpocetine increases blood circulation in the brain. In three studies of older adults with memory problems associated with poor brain Corbis circulation or dementia-related disease, vinpocetine produced improvements in performance on cognitive tests measuring BUYERS BEWARE: Researchers have not found convincing evidence attention, concentration and memory. that dietary supplements can enhance memory. CHUCK SAVAGE

90 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. risks, particularly at the typical doses of 120 to 240 milligrams Because of the differences in experimental designs used to a day. Some complications have been noted, though, including test ginkgo and other treatments, it is difﬁcult to make direct subdural hematomas (clots between the skull and brain) and gas- comparisons of efﬁcacy. For instance, on a test involving mem- trointestinal problems. As is the case with most plant extracts and ory of a brief story, glucose enhanced performance in young medications, ingestion of ginkgo is at times associated with nau- adult and healthy elderly subjects by about 30 to 40 percent. In sea and vomiting. In addition, some users experience increased people with Alzheimer’s, the improvement on a similar mem- salivation, decreased appetite, headaches, dizziness, tinnitus ory test approached 100 percent, with smaller enhancements (ringing in the ears) and skin rash. Large doses may lead to or- seen on other measures. The extent of improvement in these ex- thostatic hypotension, a condition of low blood pressure some- periments is much larger than the 10 to 20 percent gain shown times seen after abrupt postural changes, such as standing up af- with ginkgo. But most of the experiments testing the effects of ter being seated. Still, the general impression is that the incidence glucose have used short-term treatments and compared per- of serious adverse consequences after use of ginkgo is quite low. formance before and afterward, whereas most of the experi- Also, this incidence may be reduced further if and when optimal ments testing ginkgo have used long-term treatments and com- individual dose regimens for ginkgo are established. pared ginkgo-treated subjects with a control group. Does ginkgo biloba in fact enhance cognitive function? The proof for even a MILD BENEFIT is weak.

But to return to our original question, does ginkgo biloba Establishing direct comparisons of efficacy is vital to identi- in fact enhance cognitive function? In general, the reported ef- fying which treatments improve cognition the most. This is one fects are rather small. The number of experiments is also small, of many instances in which further studies of rodents would be and they are of mixed quality, so the proof for even a mild ben- useful because of the researchers’ ability to control all the vari- efit is weak. In humans, ginkgo may slow cognitive decline dur- ables in the experiment. Only one study has directly compared ing dementia. It is possible that ginkgo’s main effects on mem- the effects of ginkgo with those of other treatments. This study ory kick in after one dose and are relatively short-lived, but the showed that the peak enhancement observed with ginkgo was research literature is so limited that significant issues such as this about half of that seen with other drugs. More direct compar- one cannot be adequately evaluated at this time. isons, in both humans and lab animals, are clearly needed. We began our survey of the research literature with healthy The Bottom Line skepticism but with a commitment to avoid prejudging the find- GIVEN THE AVAILABLE EVIDENCE, is ginkgo biloba the ings. We found evidence supporting the view that ginkgo en- best therapy for improving memory? Other supplements have hances cognitive functions, albeit rather weakly, under some been found to influence cognitive function in humans and lab conditions. Our overriding impression, however, is that we do animals [see box on opposite page]. Pharmaceuticals such as not have enough information to say conclusively whether gink- donepezil can strongly enhance learning and memory in rodents go does or does not improve cognition. There are too few ex- and induce modest though significant improvements in humans. periments on which to base clear recommendations, and most But relatively simple interventions can produce some of the same of the studies showing benefits have involved too few subjects. results. For example, hearing an exciting story apparently re- But there are enough positive findings, perhaps just enough, leases epinephrine from the adrenal glands into the circulation, to sustain our interest in conducting further research on ginkgo. thereby enhancing one’s memory without any drugs at all. One Many years of experience with investigations of new drugs have mechanism by which epinephrine might enhance memory is by demonstrated that the initial positive results from studies in- liberating glucose from stores in the liver, thereby increasing the volving a small number of subjects tend to disappear when the circulating glucose available to the brain. drugs are tested in larger numbers of subjects from diverse pop- Eating a simple sugar can also improve one’s memory. Con- ulations. So the true test of ginkgo’s efficacy lies ahead. siderable evidence indicates that glucose administered system- ically (to humans by ingestion and to rodents by injection) en- MORE TO EXPLORE hances cognitive performance in young and elderly rats, mice A more detailed version of this article appeared as “Ginkgo Biloba: A and humans, including people with Alzheimer’s. Like most Cognitive Enhancer?” by Paul E. Gold, Larry Cahill and Gary L. Wenk in treatments that improve memory, glucose’s effects follow a Psychological Science in the Public Interest, Vol. 3, No. 1, pages 2–11; May 2002. Available at www.psychologicalscience.org/journals/pspi/3–1.html dose-response curve in the shape of an inverted U. Only inter- More information about ginkgo biloba and other dietary supplements can mediate doses improve memory; low doses are ineffective, and be found at dietary-supplements.info.nih.gov/ and high doses may actually impair memory. www.cfsan.fda.gov/~dms/supplmnt.html

TRANSDERMAL DRUG DELIVERY Potent Patches

Swallowing a pill is simple. Yet people still forget to take their medication, and drug levels in the bloodstream surge and sink with each dose. Medicated patches that stick to the skin prevent such problems. “The patch” became popular around 1990, as Backing smokers used it to kick the habit. A series of patches Drug-in-adhesive worn over several weeks’ time supplied decreasing amounts of nicotine, gradually weaning people from Liner their addiction. Today transdermal patches deliver es- SINGLE-LAYER PATCH trogen for hormone replacement therapy, nitroglyc- has an adhesive polymer layer that erin for angina, scopolamine for motion sickness and sticks to the skin and also holds the seasickness, fentanyl for pain control, clonidine for hy- drug. Like all currently approved pertension and, recently, ethinylestradiol plus norel- patches, it has a protective backing gestromin for contraception. and a liner that seals in the drug until In most cases the patch is saturated with the drug, a person peels it off for application. which steadily diffuses through microscopic gaps be- The diffusion rate depends on the tween skin cells and through the skin’s pores. The drug concentration in the patch, the trick is designing the appropriate polymer adhesive lipid concentration in the skin, and that will retain a given drug molecule yet also allow the skin area covered. it to diffuse, a delicate balancing act, notes Sharon Grosh of 3M Drug Delivery Systems. The skin’s outer layer of dead cells—the stratum corneum—is a good barrier, so it controls the diffusion rate. Drug molecules must be small enough to sneak between the cells and must dissolve in the oily lipids DRUG MOLECULES there, so they can reach capillaries deeper in the skin. from a patch diffuse through the lipids Furthermore, the stratum corneum varies in thickness between dead cells in the skin’s stratum and porosity from person to person, so it is advanta- corneum and past living cells in the geous if a drug has a big therapeutic window—not too Drug epidermis to capillaries in the dermis, toxic at a high concentration yet still potent at a low where they enter the bloodstream. one, says Mark R. Prausnitz of the Georgia Institute of Technology. Because of these vagaries, only a handful of drugs are effective in patch form. Researchers are trying to modify the passive patch with active drivers that force molecules that are larger or water-soluble, or both—such as insulin and vaccines—through the skin. Electric current from a tiny battery within the patch could widen cell gaps and push ionized drug molecules through them. Or an ar- Nerve ray of hollow microneedles on the patch could provide microscopic funnels through the skin. The active designs are costlier and bulkier than passive patches, but several are already in advanced clinical trials.

—Mark Fischetti ALICE Y. CHEN

92 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. ➤ THROW IT AWAY: A patch lasts only so many hours or days before its ➤ THICK-SKINNED: The stratum corneum is thickest on the palms and drug delivery falls below an effective threshold. The patch must then soles; it is thinnest behind the ear, in the armpit and on the scalp. The be removed, but it still contains medication. Users must therefore be region behind the ear is also rich with blood vessels, so it is an excel- W... certain that children or pets don’t accidently ingest the patch, which lent place for a patch, although only small designs will fit there. The O could be toxic or even fatal. armpit and scalp are generally unsuitable because hair interferes.

KN Most patches end up on the arm, inner thigh, lower back or chest, ➤ U MAX VACCINE: Certain vaccines—including those for HIV and in- where they can remain hidden and are unlikely to be rubbed off. fluenza—may elicit a strong immune response in Langerhans im- YO mune cells in the epidermis. But hypodermic needles and pills miss ➤ NO PAIN? The microneedles on experimental patches don’t hurt, D this target, sending vaccine to the bloodstream. If patches can be de- yet developers are worried that the name will scare away customers.

DI veloped to handle vaccine molecules, which are large, they could Their synonyms—microprojections, microblades—sound no better. bathe Langerhans cells, maximizing the vaccines’ effectiveness. A euphemism is sure to be found once trials are completed.

Backing Drug-in-adhesive Backing Membrane Reservoir and Drug-in-adhesive adhesive Liner Microprojection MULTILAYER PATCH MICRONEEDLE PATCH array has a membrane that controls the retains drugs in a liquid or polymer delivery rate of drugs, especially reservoir. Hollow, micromachined those that would otherwise diffuse needles penetrate the top edge of too quickly into the skin. the dermis—deep enough to bring drugs to capillaries but not so deep that they touch nerve endings, causing pain.

Stratum corneum

Epidermis

Drug

Microneedle Dermis

Capillaries

Have a topic for a future column? Send it to [email protected]

Screen Writing THE TABLET PC IS A HIGH-TECH TOOL FOR SCRIBBLERS BY MARK ALPERT

DIGITAL DOODLES can soft’s WinPad, among others—was suc- be drawn on the cessful. The biggest problem was that the Toshiba Portégé 3500. devices’ handwriting-recognition soft- You can rotate the ware did not work as well as advertised. screen 180 degrees and fold it back over Cartoonist Garry Trudeau lampooned the keyboard. the technology in a Doonesbury strip; when Mike Doonesbury scribbles “I am writing a test sentence” on the screen, the computer translates it to “Ian is riding a taste sensation.” But PC hardware and software have advanced dramatically in the past 10 years, and last November Microsoft took another stab at pen computing when it introduced a software platform for a device called the Tablet PC. Competing models of this portable machine are being man- ufactured by Toshiba, Fujitsu, Compaq, Acer and other companies, but they all share an enhanced version of Microsoft’s Windows XP operating system. As a result, the Tablet PC can incorporate handwriting into a wide variety of Windows- compatible programs; for example, you can mark up a Microsoft Word file with When I was starting out in the journal- ed by looming stacks of legal pads that scrawled comments, then e-mail the re- ism business 19 years ago, I got a piece of cover nearly every square inch of my dis- vised document via Microsoft Outlook. good advice from my first boss, Poody ordered office. Intrigued, I asked several of the manufac- Walsh, who was the editor of the Eagle Since the early 1990s computer mak- turers to let me try out their Tablet PCs, Times in Claremont, N.H. Poody (yes, ers have tried to wean me from my de- and two machines soon came to my office. believe it or not, that’s what everyone pendence on paper. Their solution was The first to arrive was the Toshiba called him) saw that I was handwriting called pen computing: I could use a sty- Portégé 3500, a 4.1-pound, $2,300 device my notes while I interviewed sources on lus to jot my notes on the screen of a that at first glance looks like an ordinary the telephone, and he urged me to get ac- portable PC, and the device’s software laptop. Conforming to the traditional customed to typing the notes instead. But would convert my chicken scratches to clamshell design, it opens to reveal a 12- I just couldn’t do it—typing seemed to re- crisp, clear text files that could be stored inch screen and a full-size keyboard. quire more brainpower than handwrit- on a hard drive instead of cluttering my When you boot it up, you see a standard ing, making it difficult to concentrate on office. Unfortunately, none of the first- Windows display. But you can turn the the interview. Two decades later I’m suf- generation pen computers—Go Corpo- Portégé into a tablet by rotating the screen

fering the consequences: I am surround- ration’s EO, Apple’s Newton and Micro- 180 degrees and folding it back over the COURTESY OF TOSHIBA

94 SCIENTIFIC AMERICAN APRIL 2003 COPYRIGHT 2003 SCIENTIFIC AMERICAN, INC. keyboard. The image on the screen suddenly shifts from a horizontal to a vertical orientation. If you pick up the device, it feels like an unusually heavy clipboard. All you need do now is pop out the tablet pen, a thin black cylinder with a white plastic tip, from its convenient niche. The tablet pen acts as the system’s mouse. You point the pen’s tip to the part of the screen where you want the cursor to go, and you tap on the icons to open files and programs. The really cool feature is that you don’t have to actually touch the screen to move the cursor. As long as the pen’s tip is within about an inch of the screen’s surface, it can control the cursor’s movements. The explanation for this “spooky action at a distance” (to borrow a term from quantum mechanics) is that a grid of wires underneath the screen emits an electromagnetic field that causes a coil inside the pen to oscillate at a res- onant frequency. These oscillations produce signals that are detected by the grid. The electromagnetic resonance technology allows you to rest your hand on the screen without affecting it. Because the system knows where the tip of the pen is, it can distinguish between a pen stroke and the pressure of a finger or thumbnail. (You’d better not lose that pen, though.) The program that best demonstrates the capabilities of the Tablet PC is Win- dows Journal. When you open this application, an image of a lined sheet of notebook paper appears on the screen. Writ- ing on this surface with the tablet pen feels very much like writing on paper with a fine-point marker. But this marker is in- credibly versatile. You have a wide choice of colors for the ink. A simple tap on an icon turns the pen into a highlighter. The other end of the pen is an electronic eras- er—you can rub it on the screen to remove your slipups. And you can cut and paste the document by drawing rings around the parts you want to move. The machine was great fun to play with (I drew some elaborate doodles), but

I wondered how well it would work dur- translating my notes. The Portégé made ing an actual interview. As a test, I jotted a few mistakes—turning “frequency” notes on the Portégé’s screen while I into “regency,” for instance—but overall spoke on the telephone with Craig Mark- the recognition was surprisingly accu- ing, a senior product manager at Toshiba. rate. The only drawback was that the It took me a moment to adjust, but after machine could convert just one page of a few minutes I was scribbling like a fiend. handwriting at a time, so creating a text I discovered, to my delight, that if you file for a long interview was frustrating- cross out a misspelled word, it automati- ly laborious. cally disappears. And there are various The other Tablet PC that I evaluated shortcuts that make reviewing the docu- was the $2,200 Fujitsu Stylistic ST4000, ment just as easy as flipping through the which works much like the Portégé but pages of a legal pad. looks less conventional. Instead of being incorporated into a folding clamshell, the screen and computer are contained in a single slab. Because the Stylistic is about a pound lighter than the Portégé, it’s easier to carry in one hand like a legal pad or clipboard. But the Stylis- tic’s screen is a bit smaller than the Portégé’s, its microprocessor is less powerful, and it doesn’t have a built-in keyboard (it comes instead with a keyboard that can be plugged in). Tablet PCs are perhaps most useful for people who take a lot of notes while on the go: journalists, college students, insurance ad- justers and so on. Although I nom- TAKING NOTES on the Fujitsu Stylistic ST4000 is fun, inally fall into the first category, I but it’s hard to beat the convenience of pen and paper. doubt that I’ll actually buy one of the devices. The problem is, I’m But being just as good as a legal pad just as disorganized in the electronic is hardly good enough to justify a $2,300 realm as I am in the world of pen and pa- purchase. The real test was how well the per. After only a few days of using the Portégé could convert my notes to text. Toshiba and Fujitsu machines, I’d clut- Earlier pen computers such as Apple’s tered up their hard drives with a bewil- Newton were designed to recognize a dering array of files. Finding my interview user’s handwriting by learning the quirks notes (either the handwritten Windows of his or her penmanship. The Tablet PC, Journal files or the converted Microsoft though, takes a brute-force approach: it Word documents) took about as long as compares each scrawl with a database rummaging through the mounds of fold- containing hundreds of thousands of ers scattered across my desk. handwriting samples. For example, the And did the digital note-taking some- software can interpret a sloppily scribed how improve the quality of this column? “it” because many poorly written “it”s I don’t know. Judging from my editor’s are stored in the database. scrawled comments (“NO, NO, NO! RE-

This technique worked quite well in WRITE!”), I guess not. CREDIT COURTESY OF FUJITSU

Was Light Faster in the Past? A MAVERICK PHYSICIST POSITS THE POSSIBILITY—AND MUCH MORE BY PHILIP MORRISON

4-D curved spacetime? Why is its content temperature is seen at every point of the FASTER THAN THE SPEED OF LIGHT: so uniform on large scale? sky to better than one part in 100,000. THE STORY OF In 1980 Alan H. Guth of the Massa- Your coffee cream confirms: uniformity A SCIENTIFIC chusetts Institute of Technology found a in fluids comes from stirring. It is easy to SPECULATION unitary explanation for both riddles. believe that those photons broke free of by João Magueijo Named inflation, it postulates a minute the expanding opaque plasma, to stream Perseus Publishing, interval of unusually sudden spatial ex- along while much slower action built the Cambridge, Mass., pansion immediately before the slow, lumpy, gravitating assemblages we call 2003 ($26) steady expansion of space carried all mat- galaxies. The time of that breakout was ter outward. That transient field eventu- a rough half a million years after the inally decayed to yield the complex mix of flationary flash. Breaking the old speed limit posted by particles (including radiations) that still It is the minor deviations from sim- one Albert Einstein in his 20s, this book move through space. The early push is plicity that give us any early detail. For deploys a racy and provocative text to maintained in the Hubble expansion ob- the past half a dozen years, the task has convey its popularized content of a new servably under way, now quite likely been to analyze all those minor flaws as cosmology. Jocular, ironic, witty, self- speeding up. hints of the earliest matter and of its centered, even indignant, Magueijo is all This very cosmos was in fact de- changes and motions as our present cos- too ready to castigate his adversaries, scribed well before any of its complex mos grew. There are no new real puzzles, those comfortable gatekeepers of learn- contents were known. In 1918 Einstein although certainly a great deal remains to ing. The author is no aspiring youth but and his friend the Dutch astronomer be learned—most importantly, the dark, a tenured professor of theoretical phys- Willem de Sitter found the broad space enigmatic legacy of AE: his cosmological ics, age 35. In spite of his own stature and time properties we now believe. In- “constant.” within learned gates—University of Lis- flation is the repulsive side of gravity’s at- The book at hand is a People’s Man- bon, then Cambridge on a prime fellow- traction, a kind of matter that stretches ifesto by an articulate and inventive op- ship, now enjoying tenure at great Impe- cosmic space so fast and far that almost rial College in London—his voice is em- every flaw has been ironed out to ap- bittered. This journey of youthful success proximate local flatness. Our current par- is recalled in complaint about the idiots, ticle physics allows such behavior, mak- the sexually deficient, the money wasters. ing such a surprise acceptable. Today we The thin volume is studded with familiar freely use what seemed unrealizable in four-letter words, invoked with rude those days. claims about the motives of colleagues, Nobody would have believed the ac- shadowy referees, editors and others count Einstein and de Sitter arrived at

tjp/CBI/press/press.html encountered. had it not ﬁtted so neatly what we ob- ~ Our current scenario for cosmology serve. Before and beyond all the starry clearly opened its second act among the galaxies, we see a distant uniform sur- high simplicities of the 1970s with two face, the origin of almost all cosmic pho- visible puzzles. Why is 3-D cosmic space tons, pure thermal radiation with utter COSMIC MICROWAVE BACKGROUND RADIATION can provide observational tests of João Magueijo’s accurately ﬂat (like old Euclid’s own), al- conformity to the established spectrum theory that the speed of light is variable.

www.astro.caltech.edu/ though it lies within Einstein’s universal shape of old Max Planck’s. The same

position to the complacent consistency I THE EDITORS RECOMMEND have just expressed. The author and his THE GEOGRAPHY OF THOUGHT: HOW ASIANS AND WESTERNERS colleagues are now skeptical of inflation: THINK DIFFERENTLY ... AND WHY it is a tale much too pat, an expansion at by Richard E. Nisbett. Free Press, New York, 2003 ($24) unlimited speed. To stir the dense, hot Nisbett, a psychologist and Distinguished University Professor at the mix in the early epochs, you have to race University of Michigan at Ann Arbor, used to believe that “all human groups and beat light itself out to the remote perceive and reason in the same way.” A series of events and studies led him boundaries of inflation. Faster than light? gradually to quite another view, that Asians and Westerners “have main- Einstein and his partner admitted only tained very different systems of thought for thousands of years.” Different one way this could happen: with repul- how? “The collective or interdependent nature of Asian society is consistent sive gravity. It is in their theory! with Asians’ broad, contextual view of the world and their belief that events Perhaps there is another way, suggests are highly complex and determined by many factors. The individualistic or Magueijo. If matter in motion is too slow independent nature of Western society seems consistent with the Western focus on for light, why not make the speed of light particular objects in isolation from their context and with Westerners’ belief that they can faster and faster into the past? Throwing know the rules governing objects and therefore can control the objects’ behavior.” Nisbett out heavyweight Einstein and his near explores areas that manifest these different approaches—among them medicine, law, constant speed of light is no easy task. science, human rights and international relations. Are the societal differences so great Yet that is the burden of the new icono- that they will lead to conflict? Nisbett thinks not. “I believe the twain shall meet by virtue clasts. Maybe they can make a cosmos of each moving in the direction of the other.” with wildly varying speeds of light, and maybe they can keep the gas uniform, WHEN SMOKE RAN LIKE WATER but they give no clear reward for so deny- by Devra Davis. Basic Books, New York, 2002 ($26) ing our well-tested Einstein on this theo- Davis tackles the subject of environmental pollution on two fronts, one rist’s journey into the past. Their strong- personal and one professional. The first contains insight into her own life, est argument is the very flatness of space: starting from her roots in the metalworking town of Donora, Pa.—where it turns out that a cosmos with a chang- the smog from pollution killed 20 outright in October 1948 and had ing speed of light must be a flat one and lasting ill effects in townspeople, some fatal, in the months and years a uniform one as well, if energy is to be that followed. Her vivid descriptions of deadly smog in London as recent conserved. There is much more to be said as the mid-1950s give the reader perspective about the inherent perils of about the untested physics of these vari- industrial pollution to the public at large. An epidemiologist by training, Davis also able vacuum light speeds. More than one chronicles the growing awareness of the spread of breast cancer (and pollution as a form of theory is out there, to say noth- possible cause) in the 1990s, sterility and testicular cancer in men, and the impact of ing of the myriad options opened by mul- pollution on climate change. Although her prose relies heavily on statistics and historical tiple dimensions. accounts of pollution, Davis’s personal narrative ties the story together nicely. Magueijo sums up with the view that the AE establishment “think they own DODO: A BRIEF HISTORY us; we think ... they are just a bunch of by Errol Fuller. Universe Publishing/Rizzoli, New York, 2002 ($22.50) squares.... We have all the fun in the uni- Sailors from a group of Dutch ships that reached the Indian Ocean island of Mauritius in verse.” I hope my comments demonstrate 1598 found dodo birds in considerable numbers along the coast. that his last remark is wrong; there is fun Forty years later the species was all but gone there, and by 1690 it with Einstein, too, plus plenty of impres- was extinct everywhere. Fuller, a British painter interested in sive experimental support. As for the true curiosities of natural history, tells the dodo’s story with grace and prize, the grandeur of cosmology, neither many intriguing illustrations. Hard facts about the dodo are minimal. the Academy nor its clever hecklers have The bird was “a gigantic, flightless pigeon” with a massive beak, a yet grasped its origins. large head and a tuftlike tail. But its exact appearance is uncertain because drawings made while it still lived are contradictory. Written Philip Morrison, professor of physics accounts are “as tantalizing as the pictures.” Having set out the few facts, Fuller (emeritus) at the Massachusetts goes on to describe the dodo’s popularity in literature—and to give it an epitaph as “the Institute of Technology, wrote the book ultimate symbol of what can go wrong when man and nature come together.” reviews and the Wonders column for All the books reviewed are available for purchase through www.sciam.com this magazine for 35 years.

The Graph of Life BY DENNIS E. SHASHA Answer to Last Month’s Puzzle The history of life is often represented by a tree, only the species we see. One more constraint: no To guarantee opening the 10-switch safe, with each existing species evolving directly from a species can arise before its progenitors appear. you need to try only single progenitor species. The newer species arises Warm-up: Assume we have three source species the combinations after some population of the original species adapts with traits ABF, BCD and ACE, respectively, and below. The first letter to different conditions and diverges genetically so three derived species with traits ACF, DEF and in each row is the much from the original group that the two can no BDE. Construct a derivation scheme that gives each setting of the first switch, the second longer mate. That’s the standard story, but biolo- derived species at most two direct progenitors (one letter is the setting of gy eschews absolutes. Many studies suggest that al- or both of which may be derived). One solution is the second switch, though individuals from different species normally depicted below. In that solution, ACF and BDE had and so on. The letter A do not interbreed, they may interbreed. What is to arise before DEF could appear. According to the stands for high more, such interbreeding, or hybridization, occa- rules above, a direct derivation of DEF from the setting, B for middle and C for low. X means sionally yields new species. source species would require all three of those spe- any setting is okay. Suppose you are trying to trace the origins of a cies—ABF, BCD and ACE—to cover all the traits. 1. A A A A A A A A A A collection of species, some of which are known to Puzzle: Suppose four source species have the 2. A B B B B B B B B B be source, or founder, species and others of which traits AB, DH, EF and CG, and the derived species 3. A C C C C C C C C C are known to be derived. For this puzzle, we want have traits BEF, DEF, ADE, ACD, ACF, ADG, 4. B A B C A B C A B C each derived species to have as few direct evolu- BEG and FGH. Construct a derivation scheme in 5. B B C A B C A B C A tionary progenitors as possible. The direct evolu- which each derived species, except one, has only 6. B C A B C A B C A B 7. C A C B A C B A C B tionary progenitors of species X are those species two direct evolutionary progenitors. (As in the 8. C B A C B A C B A C in the collection that combine to supply X’s traits warm-up, one or both may be derived.) Can you 9. C C B A C B A C B A without the involvement of any other species. Note ﬁnd four alternative source species, each having two 10. X A A A B B B C C C that three species may combine to form a new spe- traits, such that (a) every derived species here has 11. X A A A C C C B B B cies, Y, by ﬁrst producing unseen intermediate spe- only two direct progenitor species and (b) the path 12. X B B B A A A C C C 13. X B B B C C C A A A cies. Species Y would then be considered to have from a source species to a derived species goes 14. X C C C A A A B B B three direct progenitors, though, because we count through at most one other derived species? 15. X C C C B B B A A A ABF Dennis E. Shasha is professor of computer science Web Solution A at the Courant Institute of New York University. For a full explanation and the answer to F B this month’s puzzle, ACF visit www.sciam.com A BCD F DEF TRAITS OF INTEREST A = Long beak C C B B = Rainbow belly C = Long wings D BDE F ACE D = Blue eggs A E E = Long legs D F = Long tail B

C E ONE SOLUTION TO THE WARM-UP PROBLEM: ACF derives directly from E D ABF and BCD, BDE from BCD and ACE, and DEF from ACF and BDE. CREDIT MATT COLLINS

Truth in Advertising THERE ARE BURGER JOINTS, AND THEN THERE ARE BURGERS AND JOINTS BY STEVE MIRSKY

The fault, Shakespeare once almost said, entitled to purchase them, and that the is- cause it sure looks to me like an antigun lies not in our stars but in our stuffing our sue should be one of health, not the crim- commercial. I grew up in a house with a faces. That sentiment is basically the rea- inal law.” rifle, which was dismantled and in a soning behind a federal district court Which brings us to Item Two, name- locked case, and I know that no card-car- judge’s January dismissal of a recent law- ly, the current odd ad campaign spon- rying member of the National Rifle As- suit against McDonald’s, brought by two sored by the Office of National Drug sociation would keep a handgun loaded obese New York City teenagers who Control Policy. My favorite in this series and easily accessible, especially in a home claimed that the fast food was at fault for of public-service spots features two with children. Furthermore, I put forth their fat. “Common sense has prevailed,” teenage boys smoking marijuana in the the proposition that I would much rather read a statement issued by a no doubt re- den of what appears to be an upper-mid- find myself in a room full of stoned lieved McDonald’s, which had probably teenagers without guns than in a room contemplated a future where “over 99 full of straight teenagers carrying loaded billion served” would include the word weapons. (I actually did the first part of “subpoenas.” this experiment in the 1970s, but I cate- “The plaintiffs have alleged that the gorically refuse to do the second part, un- practices of McDonald’s in making and less the teenagers in question are in boot selling their products are deceptive and camp at Parris Island.) that this deception has caused the minors Now, before I get audited, no one is who have consumed McDonald’s prod- suggesting that teenagers use drugs, just ucts to injure their health by becoming as no one is suggesting that they drink obese,” observed Judge Robert W. Sweet beer until they puke, except for compa- in his ruling. In other words, the kids nies that do extensive advertising to col- asked, how were we to know that a lege kids, most of whom are below the le- steady diet of hamburgers and french gal drinking age. But I digress. Why not fries was going to make us fat? And the let teenagers know about the dangers of judge’s response was, well, they should drug use in a way that would actually get know and they therefore “cannot blame their attention? McDonald’s if they, nonetheless, choose For example, a TV commercial that to satiate their appetite with a surfeit of might very well drive many teenage boys supersized McDonald’s products.” away from marijuana could say: “Smok- Sweet clearly came down on the side dle-class home. After some insipid pot-in- ing a lot of pot may give men breasts of personal responsibility, a stance he has spired conversation, one dumb kid finds worthy of the Sports Illustrated swimsuit long taken. “In the interest of consisten- a handgun. The other dumb kid says, issue.” I can envision another commer- cy and integrity,” he wrote in a footnote, “Cool,” and asks if it’s loaded. The first cial that ends with a sober guy telling his “it should be noted that the author of this dumb kid points the gun at the second, stoned buddy, “Look, there’s not enough opinion publicly opposed the criminal- says, “No,” and pulls the trigger. We hear dope in the world to get her to sleep with ization of drugs.... This belief is based a gunshot as the screen goes dark and you.” And finally, how about one in upon the notion that, as long as con- then read the following: “Marijuana can which two fat stoners sue their dealer be- sumers have adequate knowledge about distort your sense of reality. Harmless?” cause the munchies made them eat too

even harmful substances, they should be This is an antidrug commercial? Be- much McDonald’s? ILLUSTRATION BY MATT COLLINS; PHOTOGRAPH FRANK VERONSKY

What is the importance of this recent Qscientific discovery? —Mervin Stykes, Cretin-on-Hudson, N.Y. Norman Sansperson, professor of applied heuristics at the Uni- ize individual atoms but also move them like pieces on a chess- versity of Winnepassaic, offers this perspective: board. By a happy coincidence, NASA investigators had been de- Since the dawn of time, people have wondered about this veloping a new set of algorithms for use with data from the Hub- seemingly insoluble problem. Clay tablets unearthed during the ble Space Telescope. The combination of these techniques in the 1920s in Mesopotamia indicate that the Sumerians expended mid-1990s gave us the serendipitous key we needed. considerable effort on it in 2500 B.C.; it might even have indi- The new discovery is not without controversy. Protesters— rectly influenced their development of cuneiform script. particularly in Europe—have Paracelsus and other European alchemists regarded it as announced their opposition to a problem equal to the transmutation of lead into any application of this work gold. Even Leonardo da Vinci seems to have to the genetic modification of dabbled in finding an answer, if we are food crops. Industry lobbyists to believe pages 31 through 35 of argue that the work is too pre- his notebook known as the Codex liminary for Congress to pass Worcester (he disguised his spec- the proposed regulations. And ulations with lemon juice and the global-warming implica- mirror writing to keep them from tions are especially troubling. More the prying eyes of the Church). research is needed. Clearly, we have not been able to find an answer fast enough! The recent announcement marks a clear breakthrough in our understanding. Although not all the pieces have yet Hey, what was that? dropped into place, scientists are now cautiously optimistic that —Miller Huntington, Afteryew, Miss. a final answer may soon be within reach. More research will of Q Irene Adler Holmes, manager of the Mycroft Coffee Shop, course be needed, but this basic research discovery holds the explains: potential to someday transform a wide variety of essential tech- Air masses warmed by the sun rise above colder air mass- nologies. Some analysts predict that it could give birth to a ma- es, leaving zones of low pressure. In the Northern Hemisphere, jor growth industry for the 21st century. lateral currents of air spiraling counterclockwise fill the result- To understand what has recently been learned, an analogy ing depression. It was probably the wind. may be useful. Picture the interstate highway system of the U.S. but, in place of automobiles, imagine that the roads are covered with mice. Some of these mice are painted red, others blue, others yellow, but they are all running in straight lines at 100 miles Which month is cruelest? an hour. If some force were to stretch sections of the road like Q —I. Newton, Cambridge, England taffy, the mice would move farther apart but would not lose T. S. Eliot, treasurer of the Dead Poets Society, replies: any of their information-carrying capacity. April is the cruelest month, breeding lilacs out of the dead Our new grasp of the situation might have proved impossi- land, mixing memory and desire, stirring dull roots with spring ble were it not for a series of advances in imaging over the past rain. November, also very bad. 20 years. (Poor Leonardo! Even 200 hand lenses could not have given him sufficient magnification!) Atomic force microscopy For genuinely authoritative answers to much better questions

ILLUSTRATION BY MATT COLLINS has improved so dramatically that we can now not only visual- than these, visit www.sciam.com/askexpert